POLG_ALKV
ID POLG_ALKV Reviewed; 3416 AA.
AC Q91B85;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 150.
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 Alkhumra hemorrhagic fever virus (ALKV) (Alkhurma hemorrhagic fever virus).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=172148;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=34626; Hyalomma dromedarii (Camel tick).
OH NCBI_TaxID=69826; Ornithodoros savignyi (African eyed tampan) (Soft tick).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC RNA].
RC STRAIN=1176 {ECO:0000312|EMBL:AAL08421.1};
RX PubMed=11554750; DOI=10.1006/bbrc.2001.5610;
RA Charrel R.N., Zaki A.M., Attoui H., Fakeeh M., Billoir F., Yousef A.I.,
RA de Chesse R., De Micco P., Gould E.A., de Lamballerie X.;
RT "Complete coding sequence of the Alkhurma virus, a tick-borne flavivirus
RT causing severe hemorrhagic fever in humans in Saudi Arabia.";
RL Biochem. Biophys. Res. Commun. 287:455-461(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC RNA].
RC STRAIN=1176 {ECO:0000312|EMBL:AAL08421.1};
RX PubMed=15890119; DOI=10.3201/eid1105.041298;
RA Charrel R.N., Zaki A.M., Fakeeh M., Yousef A.I., de Chesse R., Attoui H.,
RA de Lamballerie X.;
RT "Low diversity of Alkhurma hemorrhagic fever virus, Saudi Arabia, 1994-
RT 1999.";
RL Emerg. Infect. Dis. 11:683-688(2005).
RN [3]
RP ELECTRON MICROSCOPY OF THE VIRION.
RX PubMed=28051359; DOI=10.1089/vbz.2016.2064;
RA Madani T.A., Abuelzein E.M., Jalalah S.M., Abu-Araki H., Azhar E.I.,
RA Hassan A.M., Al-Bar H.M.;
RT "Electron microscopy of Alkhumra hemorrhagic fever virus.";
RL Vector Borne Zoonotic Dis. 17:195-199(2017).
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: [Serine protease NS3]:
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: [RNA-directed RNA polymerase NS5]:
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: [Serine protease NS3]:
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: [Serine protease NS3]:
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: [RNA-directed RNA polymerase NS5]:
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: [RNA-directed RNA polymerase NS5]:
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. Interacts (via N-terminus) with
CC host EXOC1 (via C-terminus); this interaction results in EXOC1
CC degradation through the proteasome degradation pathway.
CC {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. Interacts with protein prM. Interacts with non-structural
CC protein 1. {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when
CC secreted. Interacts with envelope protein E.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 2A]: Interacts (via N-terminus) with
CC serine protease NS3. {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]: 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, 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}.
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DR EMBL; AF331718; AAL08421.1; -; Genomic_DNA.
DR RefSeq; NP_722551.1; NC_004355.1.
DR SMR; Q91B85; -.
DR IntAct; Q91B85; 37.
DR MINT; Q91B85; -.
DR Proteomes; UP000136346; 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: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: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:0046718; P:viral entry into host cell; 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 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; 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; 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 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; Transferase;
KW Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW Viral immunoevasion; Viral penetration into host cytoplasm;
KW Viral RNA replication; Virion; Virus entry into host cell; Zinc.
FT CHAIN 1..3416
FT /note="Genome polyprotein"
FT /id="PRO_0000441424"
FT CHAIN 1..96
FT /note="Capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000441425"
FT PROPEP 97..117
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_0000441426"
FT CHAIN 118..281
FT /note="Protein prM"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441427"
FT CHAIN 118..206
FT /note="Peptide pr"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441428"
FT CHAIN 207..281
FT /note="Small envelope protein M"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441429"
FT CHAIN 282..777
FT /note="Envelope protein E"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441430"
FT CHAIN 778..1130
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000441431"
FT CHAIN 1131..1360
FT /note="Non-structural protein 2A"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441432"
FT CHAIN 1361..1491
FT /note="Serine protease subunit NS2B"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000441433"
FT CHAIN 1492..2112
FT /note="Serine protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000441434"
FT CHAIN 2113..2238
FT /note="Non-structural protein 4A"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000441435"
FT PEPTIDE 2239..2261
FT /note="Peptide 2k"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000441436"
FT CHAIN 2262..2513
FT /note="Non-structural protein 4B"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000441437"
FT CHAIN 2514..3416
FT /note="RNA-directed RNA polymerase NS5"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000441438"
FT TOPO_DOM 1..99
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 121..243
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 244..261
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 262
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 263..281
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 282..728
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 729..749
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 750..756
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 757..777
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 778..1134
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1135..1155
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1156..1162
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1163..1183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1184..1189
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1190..1210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1211..1235
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1236..1256
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1257..1295
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1296..1316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1317..1361
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1362..1379
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1380..1384
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1385..1405
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1406..1458
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 1459..1479
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1480..2162
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2163..2183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2184..2191
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2192..2211
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2212
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2213..2233
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2234..2246
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2247..2267
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2268..2301
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2302..2322
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2323..2345
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2346..2366
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2367..2368
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2369..2389
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2390..2432
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2433..2453
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2454..2476
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2477..2497
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2498..3416
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1492..1671
FT /note="Peptidase S7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT DOMAIN 1677..1833
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 1844..2002
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 2514..2778
FT /note="mRNA cap 0-1 NS5-type MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT DOMAIN 3042..3191
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 379..392
FT /note="Fusion peptide"
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT REGION 1412..1451
FT /note="Interacts with and activates NS3 protease"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859"
FT REGION 2732..2736
FT /note="Interaction with host SCRIB"
FT /evidence="ECO:0000250|UniProtKB:Q01299"
FT MOTIF 1781..1784
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT ACT_SITE 1545
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1569
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1629
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 2574
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2659
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2696
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2732
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 1690..1697
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 2569
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 2600
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 2618
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 2645
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 2734
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2952
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 2956
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 2961
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 3226
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 3242
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 3361
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 97..98
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 118..119
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 206..207
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 281..282
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 777..778
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 1130..1131
FT /note="Cleavage; by host"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1360..1361
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1491..1492
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 1951
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 1954
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 2112..2113
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 2238..2239
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 2261..2262
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 2513..2514
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 2526
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2529
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2530
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2532
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2537
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2541
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2574
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2659
FT /note="Essential for 2'-O-methyltransferase and N-7
FT methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2663
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2696
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2727
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2729
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2732
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT MOD_RES 2569
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 435
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 862
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 985
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1001
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 284..311
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 341..402
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 341..397
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 355..386
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 373..402
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 373..397
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 467..571
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 588..619
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 781..792
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 832..922
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 957..1002
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1059..1108
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1070..1092
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1091..1095
FT /evidence="ECO:0000250|UniProtKB:P17763"
SQ SEQUENCE 3416 AA; 378122 MW; EDAB88E8A9DD7A27 CRC64;
MAKGAVLKGK GGGPPRRVPK ETAKKTRQGP GRLPNGLVLM RMMGVLWHMI AGTARSPILK
RFWATVPVRQ AIAALRKIRK TVGLLLDSLN RRRGKRRSTT GLLTSILLAC LATLVISATI
RRERTGDMVI RAEGKDAATQ VEVVNGTCII LATDMGSWCD DSIMYECVTI DSGEEPVDVD
CFCRGVERVS LEYGRCGKPV GGRSRRSVSI PVHAHSDLTG RGHKWLRGDS VKTHLTRVEG
WVWKNKLLTM AFCAVVWMVT DSLPTRFIVI TVALCLAPTY ATRCTHLQNR DFVSGIQGTT
RVSLVLELGG CVTLTAEGKP SVDVWLDDIH QENPAKTREY CLHAKLASSK VVARCPAMGP
ATLPEEHQAS TVCRRDQSDR GWGNHCGLFG KGSIVACAKF ACEAKKKATG YVYDVNKITY
VVKVEPHTGD YLAANESHSN RKTASFTTQS EKTILTLGDY GDISLTCRVT SGVDPAQTVV
LELDKTAEHL PKAWQVHRDW FEDLSLPWRH EGAHEWNHAD RLVEFGEPHA VKMDIFNLGD
QTGILLKSLA GVPVANIEGS KYHLQSGHVT CDVGLEKLKM KGMTYTVCEG SKFAWKRPPT
DSGHDTVVME VTYTGSKPCR IPVRAVAHGE PNVNVASLIT PNPSMETTGG GFVELQLPPG
DNIIYVGELS HQWFQKGSTI GRVLEKTRRG IERLTVVGEH AWDFGSVGGV LSSVGKALHT
AFGAAFNTIF GGVGFLPRIL LGVALAWLGL NSRNPTLSVG FLITGGLVLT MTLGVGADMG
CAIDANRMEL RCGEGLVVWR EVTDWYDGYA FHPESPPVLA ASLKEAYEEG VCGIVPQNRL
EMAMWRRVEA VLNLALAESD ANLTVVVDRR DPSDYRGGKV GILKRSGKEM KTSWKGWSQS
FVWSVPESPR RFMVGIEGTG ECPLDKRRTG VFTVAEFGMG MRTKIFLDLR ETSSSDCDTG
VMGAAVKSGH AVHTDQSLWM KSHRNATGVF ISELIVTDLR NCTWPASHTL DNAGVVDSKL
FLPVSLAGPR SHYNHIPGYA EQVRGPWNQT PLRVVREPCP GTTVKIDQNC DKRGSSLRST
TESGKAIPEW CCRTCELPPV TFRSGTDCWY AMEIRPVHQQ GGLVRSMVLA DNGAMLSEGG
VPGIVAVFVV LELVIRRRPT TGTSVVWCGV VVLGLVVTGL VTIEGLCRYV VAVGILMSME
LGPEIVALVL LQAVFDMRTG LLVAFAVKRA YTTREAVVTY FLLLVLELGF PEASLSNIWK
WADSLAMGTL ILQACSQEGR ARVGYLLAAM MTQKDMAIIH TGLTIFLSAA TAMAVWSMIK
GQRDQKGLSW ATPLVGLFGG EGVGLRLLAF RRLAERRNRR SFSEPLTVVG VMLTVASGMV
RHTSQEALCA LVAGAFLLLM MVLGTRKMQL IAEWCGEVEW NPDLVNEGGE VNLKVRQDAM
GNLHLTEVEK EERAMALWLL AGLVASAFHW AGILIVLAIW TFFEMLSSGR RSELVFSGQG
TRTERNRPFE IKDGAYRIYS PGLLWGHRQI GVGYGAKGVL HTMWHVTRGA ALVVEEAISG
PYWADVREDV VCYGGAWSLE SRWRGETVQV HAFPPGRPQE THQCQPGELI LENGRKLGAV
PIDLSKGTSG SPIINAQGEV VGLYGNGLKT NEAYVSSIAQ GEAEKSRPEL PLSVQGTGWM
SKGQITVLDM HPGSGKTHRV LPELVRQCAN RGMRTLVLAP TRVVLKEMEK ALAGKKVRFH
SPAVEGQSTA GAVVDVMCHA TYVHRRLLPQ GRQNWEVAIM DEAHWTDPHS IAARGHLYSL
AKENRCALVL MTATPPGRGD PFPESNGAIM SEERAIPDGE WREGFDWITE YEGRTAWFVP
SISKGGAIAR TLRQRGKSVI CLNSKTFEKD YLRVREEKPD FVVTTDISEM GANLDVSRVI
DGRTNIKPEE VDGKVEMTGT RKITTASAAQ RRGRVGRTSG RTDEYIYSGQ CDDDDTSLVQ
WKEAQILLDN ITTLRGPVAT FYGPEQMKMP EVAGHYRLNE EKRKHFRHLM TQCDFTPWLA
WHVATNTSNV LDRSWTWQGP EGNAIDGADG DLVRFKTPGG SERVLQPVWK DCRMFREGRD
VKDFILYASG RRSVGDVLGG LAGVPGLLRH RCASALDVVY TLLNENPGSR AMRMAERDAP
EAFLTIVEVA VLGVATLGIL WCFVARTSVS RMFLGTVVLF AALLLLWIGG VDYGYMAGIA
LIFYIFLTVL QPEPGKQRSS DDNRLAYFLL GLLSLAGLVT ANEMGMLDKT KADLAGLMWH
GEQRHPAWEE WTNVDIQPAR SWGTYVLIVS LFTPYMLHQL QTKIQQLVNS SVASGAQAMR
DLGGGTPFFG VAGHVIALGV TSLVGATPLS LGLGVALAAF HLAIVASGLE AELTQRAHRV
FFSAMVKNPM VDGDVINPFP DGEPKPVLYE RRMSLILAIA LCMVSVVLNR TAASMTEAGA
VGLAALGQLV HPETETLWTM PMACGMAGLV RGSFWGLLPM GHRLWLKTTG TRRGGADGET
LGDIWKRRLN GCSREEFFQY RRSGVMETER DRARELLKRG ETNMGLAVSR GTAKLAWLEE
RGYATLKGEV VDLGCGRGGW SYYAASRPAV MGVKAYTIGG KGHEVPRLIT SLGWNLIKFR
TGMDVYSLEA HRADTILCDI GESNPDPLVE GERSRRVILL MEKWKLRNPD ASCVFKVLAP
YRPEVLEALH RFQLQWGGGL VRVPFSRNST HEMYFSTAVS GNIVNSVNIQ SRKLLARFGD
QRGPAKVPEV DLGTGTRCVV LAEDKVREAD VAERITALKT QYGDSWHVDK EHPYRTWQYW
GSYKTEATGS AASLINGVVK LLSWPWNARE DVVRMAMTDT TAFGQQRVFK EKVDTKAQEP
QVGTKIIMRA VNDWILERLA GKKTPRLCTR EEFIAKVRSN AALGAWSDEQ NRWSNAREAV
EDPEFWRLVD EERERHLRGR CAQCVYNMMG KREKKLGEFG VAKGSRAIWY MWLGSRYLEF
EALGFLNEDH WASRDLSGAG VEGISLNYLG WHLKRLSELE GGLFYADDTA GWDTRITNAD
LEDEEQILRY LRGEHRTLAK TILEKAYHAK VVKVARPSSS GGCVMDIITR RDQRGSGQVV
TYALNTLTNI KVQLIRMMEG EGVIGPSDSQ DPRLLRVEAW LKEYGEERLT RMLVSGDDCV
VRPIDDRFGK ALYFLNDMAK VRKDIGEWEP SEGYSSWEEV PFCSHHFHEL TMKDGRVIIV
PCRDQDELVG RARVSPGCGW SVRETACLSK AYGQMWLLSY FHRRDLRTLG LAICSAVPID
WVPQGRTTWS IHASGAWMTT EDMLEVWNRV WILDNPFMSD KGKVKEWRDI PYLPKSQDGL
CSSLVGRRER AEWAKNIWGS VEKVRRMIGP ERYADYLSCM DRHELHWDLK LESNII
