POLG_ZIKVF
ID POLG_ZIKVF Reviewed; 3423 AA.
AC A0A024B7W1;
DT 31-JAN-2018, integrated into UniProtKB/Swiss-Prot.
DT 09-JUL-2014, sequence version 1.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=Genome polyprotein;
DE Contains:
DE RecName: Full=Capsid protein C {ECO:0000250|UniProtKB:P17763};
DE AltName: Full=Capsid protein;
DE AltName: Full=Core protein;
DE Contains:
DE RecName: Full=Protein prM {ECO:0000250|UniProtKB:P17763};
DE AltName: Full=Precursor membrane protein;
DE Contains:
DE RecName: Full=Peptide pr {ECO:0000250|UniProtKB:P17763};
DE AltName: Full=Peptide precursor;
DE Contains:
DE RecName: Full=Small envelope protein M {ECO:0000250|UniProtKB:P17763};
DE AltName: Full=Matrix protein;
DE Contains:
DE RecName: Full=Envelope protein E {ECO:0000250|UniProtKB:P17763};
DE Contains:
DE RecName: Full=Non-structural protein 1 {ECO:0000250|UniProtKB:P17763};
DE Short=NS1;
DE Contains:
DE RecName: Full=Non-structural protein 2A {ECO:0000250|UniProtKB:P17763};
DE Short=NS2A;
DE Contains:
DE RecName: Full=Serine protease subunit NS2B {ECO:0000250|UniProtKB:P17763};
DE AltName: Full=Flavivirin protease NS2B regulatory subunit;
DE AltName: Full=Non-structural protein 2B;
DE Contains:
DE RecName: Full=Serine protease NS3 {ECO:0000250|UniProtKB:P17763};
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 {ECO:0000250|UniProtKB:P17763};
DE Short=NS4A;
DE Contains:
DE RecName: Full=Peptide 2k {ECO:0000250|UniProtKB:P17763};
DE Contains:
DE RecName: Full=Non-structural protein 4B {ECO:0000250|UniProtKB:P17763};
DE Short=NS4B;
DE Contains:
DE RecName: Full=RNA-directed RNA polymerase NS5 {ECO:0000303|PubMed:30951555};
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:0000269|PubMed:30951555};
DE AltName: Full=NS5;
OS Zika virus (isolate ZIKV/Human/French Polynesia/10087PF/2013) (ZIKV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=2043570;
OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OH NCBI_TaxID=7160; Aedes albopictus (Asian tiger mosquito) (Stegomyia albopicta).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9544; Macaca mulatta (Rhesus macaque).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=24903869; DOI=10.1128/genomea.00500-14;
RA Baronti C., Piorkowski G., Charrel R.N., Boubis L., Leparc-Goffart I.,
RA de Lamballerie X.;
RT "Complete coding sequence of zika virus from a French polynesia outbreak in
RT 2013.";
RL Genome Announc. 2:0-0(2014).
RN [2]
RP INTERACTION WITH HOST TYRO3 (ENVELOPE PROTEIN E), INTERACTION WITH HOST AXL
RP (ENVELOPE PROTEIN E), AND INTERACTION WITH HOST DC SIGN (ENVELOPE PROTEIN
RP E).
RC STRAIN=PF-25013-18;
RX PubMed=26085147; DOI=10.1128/jvi.00354-15;
RA Hamel R., Dejarnac O., Wichit S., Ekchariyawat P., Neyret A.,
RA Luplertlop N., Perera-Lecoin M., Surasombatpattana P., Talignani L.,
RA Thomas F., Cao-Lormeau V.M., Choumet V., Briant L., Despres P., Amara A.,
RA Yssel H., Misse D.;
RT "Biology of zika virus infection in human skin cells.";
RL J. Virol. 89:8880-8896(2015).
RN [3]
RP FUNCTION (NON-STRUCTURAL PROTEIN 4A), AND FUNCTION (NON-STRUCTURAL PROTEIN
RP 4B).
RX PubMed=27524440; DOI=10.1016/j.stem.2016.07.019;
RA Liang Q., Luo Z., Zeng J., Chen W., Foo S.S., Lee S.A., Ge J., Wang S.,
RA Goldman S.A., Zlokovic B.V., Zhao Z., Jung J.U.;
RT "Zika virus NS4A and NS4B proteins deregulate Akt-mTOR signaling in human
RT fetal neural stem cells to inhibit neurogenesis and induce autophagy.";
RL Cell Stem Cell 19:663-671(2016).
RN [4]
RP GLYCOSYLATION AT ASN-444, AND MUTAGENESIS OF ASN-444.
RX PubMed=29091758; DOI=10.1016/j.celrep.2017.10.016;
RA Fontes-Garfias C.R., Shan C., Luo H., Muruato A.E., Medeiros D.B.A.,
RA Mays E., Xie X., Zou J., Roundy C.M., Wakamiya M., Rossi S.L., Wang T.,
RA Weaver S.C., Shi P.Y.;
RT "Functional analysis of glycosylation of a Zika Virus envelope protein.";
RL Cell Rep. 21:1180-1190(2017).
RN [5]
RP FUNCTION (SERINE PROTEASE NS3), AND FUNCTION (NON-STRUCTURAL PROTEIN 4A).
RC STRAIN=ZIKV/Homo sapiens/THA/PLCal_ZV/2013;
RX PubMed=28592527; DOI=10.1128/jvi.00474-17;
RA Hou S., Kumar A., Xu Z., Airo A.M., Stryapunina I., Wong C.P., Branton W.,
RA Tchesnokov E., Goette M., Power C., Hobman T.C.;
RT "Zika virus hijacks stress granule proteins and modulates the host stress
RT response.";
RL J. Virol. 0:0-0(2017).
RN [6]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5), FUNCTION (NON-STRUCTURAL
RP PROTEIN 4A), INTERACTION WITH HUMAN STAT2 (RNA-DIRECTED RNA POLYMERASE
RP NS5), INTERACTION WITH HUMAN PAF1 COMPLEX (RNA-DIRECTED RNA POLYMERASE
RP NS5), INTERACTION WITH HUMAN SRPRA (NON-STRUCTURAL PROTEIN 4A), INTERACTION
RP WITH HUMAN SEC61G (NON-STRUCTURAL PROTEIN 4A), AND INTERACTION WITH HUMAN
RP ANKLE2 (NON-STRUCTURAL PROTEIN 4A).
RX PubMed=30550790; DOI=10.1016/j.cell.2018.11.028;
RA Shah P.S., Link N., Jang G.M., Sharp P.P., Zhu T., Swaney D.L.,
RA Johnson J.R., Von Dollen J., Ramage H.R., Satkamp L., Newton B.,
RA Huettenhain R., Petit M.J., Baum T., Everitt A., Laufman O., Tassetto M.,
RA Shales M., Stevenson E., Iglesias G.N., Shokat L., Tripathi S.,
RA Balasubramaniam V., Webb L.G., Aguirre S., Willsey A.J., Garcia-Sastre A.,
RA Pollard K.S., Cherry S., Gamarnik A.V., Marazzi I., Taunton J.,
RA Fernandez-Sesma A., Bellen H.J., Andino R., Krogan N.J.;
RT "Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms
RT of Dengue and Zika Virus Pathogenesis.";
RL Cell 175:1931-1945(2018).
RN [7]
RP SUMOYLATION (RNA-DIRECTED RNA POLYMERASE NS5), REGION (RNA-DIRECTED RNA
RP POLYMERASE NS5), SUBCELLULAR LOCATION (RNA-DIRECTED RNA POLYMERASE NS5),
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5), AND MUTAGENESIS OF LYS-2772.
RX PubMed=32699085; DOI=10.1128/jvi.01086-20;
RA Conde J.N., Schutt W., Mladinich M., Sohn S.Y., Hearing P., Mackow E.R.;
RT "NS5 Sumoylation Directs Nuclear Responses that Permit Zika Virus to
RT Persistently Infect Human Brain Microvascular Endothelial Cells.";
RL J. Virol. 0:0-0(2020).
RN [8] {ECO:0007744|PDB:5GOZ, ECO:0007744|PDB:5GP1}
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 2524-2785 IN COMPLEX WITH GTP;
RP S-ADENOSYL-L-METHIONINE.
RX PubMed=27866982; DOI=10.1016/j.bbrc.2016.11.098;
RA Zhang C., Feng T., Cheng J., Li Y., Yin X., Zeng W., Jin X., Li Y., Guo F.,
RA Jin T.;
RT "Structure of the NS5 methyltransferase from Zika virus and implications in
RT inhibitor design.";
RL Biochem. Biophys. Res. Commun. 492:624-630(2017).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 589-697.
RX PubMed=27475895; DOI=10.1016/j.cell.2016.07.020;
RA Zhao H., Fernandez E., Dowd K.A., Speer S.D., Platt D.J., Gorman M.J.,
RA Govero J., Nelson C.A., Pierson T.C., Diamond M.S., Fremont D.H.;
RT "Structural basis of Zika Virus-specific antibody protection.";
RL Cell 166:1016-1027(2016).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.33 ANGSTROMS) OF 2521-2786 IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE.
RX PubMed=27633330; DOI=10.1016/j.celrep.2016.08.091;
RA Coloma J., Jain R., Rajashankar K.R., Garcia-Sastre A., Aggarwal A.K.;
RT "Structures of NS5 Methyltransferase from Zika Virus.";
RL Cell Rep. 16:3097-3102(2016).
RN [11]
RP STRUCTURE BY ELECTRON MICROSCOPY (4.00 ANGSTROMS) OF 216-794, AND
RP GLYCOSYLATION AT ASN-444.
RX PubMed=27882950; DOI=10.1038/ncomms13679;
RA Zhang S., Kostyuchenko V.A., Ng T.S., Lim X.N., Ooi J.S., Lambert S.,
RA Tan T.Y., Widman D.G., Shi J., Baric R.S., Lok S.M.;
RT "Neutralization mechanism of a highly potent antibody against Zika virus.";
RL Nat. Commun. 7:13679-13679(2016).
RN [12]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.70 ANGSTROMS) OF 216-794, AND
RP GLYCOSYLATION AT ASN-444.
RX PubMed=27093288; DOI=10.1038/nature17994;
RA Kostyuchenko V.A., Lim E.X., Zhang S., Fibriansah G., Ng T.S., Ooi J.S.,
RA Shi J., Lok S.M.;
RT "Structure of the thermally stable Zika virus.";
RL Nature 533:425-428(2016).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 291-698 IN COMPLEX WITH
RP BETA-D-MANNOSE AND MANNOSE, AND GLYCOSYLATION AT ASN-444.
RX PubMed=27338953; DOI=10.1038/nature18938;
RA Barba-Spaeth G., Dejnirattisai W., Rouvinski A., Vaney M.C., Medits I.,
RA Sharma A., Simon-Loriere E., Sakuntabhai A., Cao-Lormeau V.M., Haouz A.,
RA England P., Stiasny K., Mongkolsapaya J., Heinz F.X., Screaton G.R.,
RA Rey F.A.;
RT "Structural basis of potent Zika-dengue virus antibody cross-
RT neutralization.";
RL Nature 536:48-53(2016).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1674-2119.
RX PubMed=27172988; DOI=10.1007/s13238-016-0275-4;
RA Tian H., Ji X., Yang X., Xie W., Yang K., Chen C., Wu C., Chi H., Mu Z.,
RA Wang Z., Yang H.;
RT "The crystal structure of Zika virus helicase: basis for antiviral drug
RT design.";
RL Protein Cell 7:450-454(2016).
RN [15]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) OF 291-794 AND 216-290.
RX PubMed=27033547; DOI=10.1126/science.aaf5316;
RA Sirohi D., Chen Z., Sun L., Klose T., Pierson T.C., Rossmann M.G.,
RA Kuhn R.J.;
RT "The 3.8 A resolution cryo-EM structure of Zika virus.";
RL Science 352:467-470(2016).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 2521-2784.
RX PubMed=28357511; DOI=10.1007/s00705-017-3345-x;
RA Hercik K., Brynda J., Nencka R., Boura E.;
RT "Structural basis of Zika virus methyltransferase inhibition by
RT sinefungin.";
RL Arch. Virol. 162:2091-2096(2017).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 2525-2786 IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE.
RX PubMed=28031359; DOI=10.1128/jvi.02202-16;
RA Coutard B., Barral K., Lichiere J., Selisko B., Martin B., Aouadi W.,
RA Lombardia M.O., Debart F., Vasseur J.J., Guillemot J.C., Canard B.,
RA Decroly E.;
RT "Zika Virus methyltransferase: structure and functions for drug design
RT perspectives.";
RL J. Virol. 91:0-0(2017).
RN [18]
RP STRUCTURE BY ELECTRON MICROSCOPY (6.20 ANGSTROMS) OF 291-686.
RX PubMed=28300075; DOI=10.1038/ncomms14722;
RA Hasan S.S., Miller A., Sapparapu G., Fernandez E., Klose T., Long F.,
RA Fokine A., Porta J.C., Jiang W., Diamond M.S., Crowe J.E., Kuhn R.J.,
RA Rossmann M.G.;
RT "A human antibody against Zika virus crosslinks the E protein to prevent
RT infection.";
RL Nat. Commun. 8:14722-14722(2017).
RN [19]
RP STRUCTURE BY ELECTRON MICROSCOPY (9.10 ANGSTROMS) OF 726-791 AND 238-290.
RX PubMed=28067914; DOI=10.1038/nsmb.3352;
RA Prasad V.M., Miller A.S., Klose T., Sirohi D., Buda G., Jiang W.,
RA Kuhn R.J., Rossmann M.G.;
RT "Structure of the immature Zika virus at 9 A resolution.";
RL Nat. Struct. Mol. Biol. 24:184-186(2017).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 2521-2788.
RX PubMed=28487506; DOI=10.1038/s41598-017-01756-7;
RA Jain R., Butler K.V., Coloma J., Jin J., Aggarwal A.K.;
RT "Development of a S-adenosylmethionine analog that intrudes the RNA-cap
RT binding site of Zika methyltransferase.";
RL Sci. Rep. 7:1632-1632(2017).
RN [21] {ECO:0007744|PDB:5NJU, ECO:0007744|PDB:5NJV}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2524-2785.
RX PubMed=29423037; DOI=10.18632/oncotarget.23223;
RA Chatrin C., Talapatra S.K., Canard B., Kozielski F.;
RT "The structure of the binary methyltransferase-SAH complex from Zika virus
RT reveals a novel conformation for the mechanism of mRNA capping.";
RL Oncotarget 9:3160-3171(2018).
RN [22] {ECO:0007744|PDB:6CO8}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.10 ANGSTROMS) OF 291-794 AND 216-290.
RX PubMed=29958768; DOI=10.1016/j.str.2018.05.006;
RA Sevvana M., Long F., Miller A.S., Klose T., Buda G., Sun L., Kuhn R.J.,
RA Rossmann M.G.;
RT "Refinement and Analysis of the Mature Zika Virus Cryo-EM Structure at 3.1
RT A Resolution.";
RL Structure 26:1169-1177(2018).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (3.98 ANGSTROMS) OF 2521-3423, SUBUNIT (RNA-DIRECTED
RP RNA POLYMERASE NS5), FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5), CATALYTIC
RP ACTIVITY (RNA-DIRECTED RNA POLYMERASE NS5), AND MUTAGENESIS OF TYR-2545;
RP LYS-2548 AND LYS-2549.
RX PubMed=30951555; DOI=10.1371/journal.ppat.1007656;
RA Ferrero D.S., Ruiz-Arroyo V.M., Soler N., Uson I., Guarne A., Verdaguer N.;
RT "Supramolecular arrangement of the full-length Zika virus NS5.";
RL PLoS Pathog. 15:e1007656-e1007656(2019).
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 the mature virus particle. During virus entry,
CC may 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 pH 6.0.
CC After virion release in extracellular space, gets dissociated from E
CC dimers. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Protein prM]: Plays a role in host immune defense modulation
CC and protection of envelope protein E during virion synthesis. PrM-E
CC cleavage is inefficient, many virions are only partially matured and
CC immature prM-E proteins could play a role in immune evasion.
CC Contributes to fetal microcephaly in humans. Acts as a chaperone for
CC envelope protein E during intracellular virion assembly by masking and
CC inactivating envelope protein E fusion peptide. prM is the only viral
CC peptide matured by host furin in the trans-Golgi network probably to
CC avoid catastrophic activation of the viral fusion activity in acidic
CC Golgi compartment prior to virion release.
CC {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 receptors
CC and mediates fusion between viral and cellular membranes. Efficient
CC virus attachment to cell is, at least in part, mediated by host HAVCR1
CC in a cell-type specific manner (By similarity). In addition, host NCAM1
CC can also be used as entry receptor (By similarity).Interaction with
CC host HSPA5 plays an important role in the early stages of infection as
CC well (By similarity). Envelope protein is synthesized in the
CC endoplasmic reticulum and forms a heterodimer with protein prM. The
CC heterodimer plays a role in virion budding in the ER, and the newly
CC formed immature particle is covered with 60 spikes composed of
CC heterodimers between precursor prM and envelope protein E. The virion
CC is transported to the Golgi apparatus where the low pH causes the
CC dissociation of PrM-E heterodimers and formation of E homodimers. PrM-E
CC cleavage is inefficient, many virions are only partially matured and
CC immature prM-E proteins could play a role in immune evasion (By
CC similarity). {ECO:0000250|UniProtKB:A0A142I5B9,
CC ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Non-structural protein 1]: Plays a role in the inhibition of
CC host RLR-induced interferon-beta activation by targeting TANK-binding
CC kinase 1/TBK1. In addition, recruits the host deubiquitinase USP8 to
CC cleave 'Lys-11'-linked polyubiquitin chains from caspase-1/CASP1 thus
CC inhibiting its proteasomal degradation. In turn, stabilized CASP1
CC promotes cleavage of cGAS, which inhibits its ability to recognize
CC mitochondrial DNA release and initiate type I interferon signaling.
CC {ECO:0000250|UniProtKB:Q32ZE1}.
CC -!- FUNCTION: [Non-structural protein 2A]: Component of the viral RNA
CC replication complex that recruits genomic RNA, the structural protein
CC prM/E complex, and the NS2B/NS3 protease complex to the virion assembly
CC site and orchestrates virus morphogenesis (By similarity). Antagonizes
CC also the host MDA5-mediated induction of alpha/beta interferon
CC antiviral response (By similarity). May disrupt adherens junction
CC formation and thereby impair proliferation of radial cells in the host
CC cortex (By similarity). {ECO:0000250|UniProtKB:A0A142I5B9,
CC ECO:0000250|UniProtKB:Q32ZE1}.
CC -!- FUNCTION: [Serine protease subunit NS2B]: Required cofactor for the
CC serine protease function of NS3. {ECO:0000250|UniProtKB:Q32ZE1}.
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 (By similarity). Leads to
CC translation arrest when expressed ex vivo (PubMed:28592527).
CC {ECO:0000250|UniProtKB:Q32ZE1, ECO:0000269|PubMed:28592527}.
CC -!- FUNCTION: [Non-structural protein 4A]: Regulates the ATPase activity of
CC the NS3 helicase activity (By similarity). NS4A allows NS3 helicase to
CC conserve energy during unwinding (By similarity). Cooperatively with
CC NS4B suppresses the Akt-mTOR pathway and leads to cellular
CC dysregulation (PubMed:27524440). By inhibiting host ANKLE2 functions,
CC may cause defects in brain development, such as microcephaly
CC (PubMed:30550790). Antagonizes also the host MDA5-mediated induction of
CC alpha/beta interferon antiviral response (By similarity). Leads to
CC translation arrest when expressed ex vivo (PubMed:28592527).
CC {ECO:0000250|UniProtKB:Q32ZE1, ECO:0000250|UniProtKB:Q9Q6P4,
CC ECO:0000269|PubMed:27524440, ECO:0000269|PubMed:28592527,
CC ECO:0000269|PubMed:30550790}.
CC -!- FUNCTION: [Peptide 2k]: Functions as a signal peptide for NS4B and is
CC required for the interferon antagonism activity of the latter.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Non-structural protein 4B]: Induces the formation of ER-
CC derived membrane vesicles where the viral replication takes place (By
CC similarity). Also plays a role in the inhibition of host RLR-induced
CC interferon-beta production at TANK-binding kinase 1/TBK1 level (By
CC similarity). Cooperatively with NS4A suppresses the Akt-mTOR pathway
CC and leads to cellular dysregulation (PubMed:27524440).
CC {ECO:0000250|UniProtKB:Q32ZE1, ECO:0000250|UniProtKB:Q9Q6P4,
CC ECO:0000269|PubMed:27524440}.
CC -!- FUNCTION: [RNA-directed RNA polymerase NS5]: Replicates the viral (+)
CC and (-) RNA genome, and performs the capping of genomes in the
CC cytoplasm (PubMed:30951555). Methylates viral RNA cap at guanine N-7
CC and ribose 2'-O positions. Once sufficient NS5 is expressed, binds to
CC the cap-proximal structure and inhibits further translation of the
CC viral genome (By similarity). Besides its role in RNA genome
CC replication, also prevents the establishment of a cellular antiviral
CC state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling
CC pathway. Mechanistically, interferes with host kinases TBK1 and IKKE
CC upstream of interferon regulatory factor 3/IRF3 to inhibit the RIG-I
CC pathway (By similarity). Antagonizes also type I interferon signaling
CC by targeting STAT2 for degradation by the proteasome thereby preventing
CC activation of JAK-STAT signaling pathway (By similarity). Within the
CC host nucleus, disrupts host SUMO1 and STAT2 co-localization with PML,
CC resulting in PML degradation (PubMed:32699085). May also reduce immune
CC responses by preventing the recruitment of the host PAF1 complex to
CC interferon-responsive genes (PubMed:30550790).
CC {ECO:0000250|UniProtKB:Q32ZE1, ECO:0000269|PubMed:30550790,
CC ECO:0000269|PubMed:30951555, ECO:0000269|PubMed:32699085}.
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 -!- 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 ECO:0000269|PubMed:30951555};
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; Evidence={ECO:0000250|UniProtKB:Q32ZE1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
CC Evidence={ECO:0000250|UniProtKB:Q32ZE1};
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 -!- SUBUNIT: [Capsid protein C]: Homodimer. {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Protein prM]: Forms heterodimers with envelope protein E in
CC the endoplasmic reticulum and Golgi (By similarity). Interacts with
CC non-structural protein 2A (By similarity).
CC {ECO:0000250|UniProtKB:A0A142I5B9, ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Envelope protein E]: Homodimer; in the endoplasmic reticulum
CC and Golgi (By similarity). Interacts with host TYRO3, AXL and DC-SIGN
CC proteins (PubMed:26085147). Interacts with non-structural protein 2A
CC (By similarity). Interacts with host HAVCR1; this interaction likely
CC mediates virus attachment to host cell (By similarity). Interacts with
CC host NCAM1 (By similarity). Interacts with host HSPA5 (By similarity).
CC {ECO:0000250|UniProtKB:A0A142I5B9, ECO:0000250|UniProtKB:P17763,
CC ECO:0000269|PubMed:26085147}.
CC -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when
CC secreted (By similarity). Interacts with host TBK1 (By similarity).
CC Interacts with host USP8 (By similarity). Interacts with envelope
CC protein E (By similarity). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000250|UniProtKB:Q32ZE1}.
CC -!- SUBUNIT: [Non-structural protein 2A]: Interacts with the structural
CC protein prM/E complex, and the NS2B/NS3 protease complex.
CC {ECO:0000250|UniProtKB:A0A142I5B9}.
CC -!- SUBUNIT: [Serine protease subunit NS2B]: Forms a heterodimer with
CC serine protease NS3 (By similarity). May form homooligomers (By
CC similarity). Interacts with human SPCS1 (By similarity). Interacts with
CC non-structural protein 2A (By similarity).
CC {ECO:0000250|UniProtKB:A0A142I5B9, ECO:0000250|UniProtKB:P17763,
CC ECO:0000250|UniProtKB:Q32ZE1}.
CC -!- SUBUNIT: [Serine protease NS3]: Forms a heterodimer with NS2B (By
CC similarity). Interacts with NS4B (By similarity). Interacts with
CC unphosphorylated RNA-directed RNA polymerase NS5; this interaction
CC stimulates RNA-directed RNA polymerase NS5 guanylyltransferase activity
CC (By similarity). Interacts with non-structural protein 2A (By
CC similarity). Interacts with host SHFL; this interaction promotes NS3
CC degradation via a lysosome-dependent pathway (By similarity).
CC {ECO:0000250|UniProtKB:A0A142I5B9, ECO:0000250|UniProtKB:P17763,
CC ECO:0000250|UniProtKB:Q32ZE1}.
CC -!- SUBUNIT: [Non-structural protein 4A]: May interact with host ANKLE2;
CC the interaction may cause defects in brain development, such as
CC microcephaly (PubMed:30550790). May interact with host SRPRA and SEC61G
CC (PubMed:30550790). {ECO:0000269|PubMed:30550790}.
CC -!- SUBUNIT: [Non-structural protein 4B]: Interacts with serine protease
CC NS3. Interacts with NS1 (By similarity).
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase NS5]: Homodimer; dimerization may
CC negatively regulate the GTase activity, a crucial step in the capping
CC process (PubMed:30951555). Interacts with host STAT2; this interaction
CC inhibits the phosphorylation of the latter, and, when all viral
CC proteins are present (polyprotein), targets STAT2 for degradation
CC (PubMed:30550790, PubMed:32699085). Interacts with host TBK1 and IKBKE;
CC these interactions lead to the inhibition of the host RIG-I signaling
CC pathway (By similarity). Interacts with host PAF1 complex; the
CC interaction may prevent the recruitment of the host PAF1 complex to
CC interferon-responsive genes, and thus reduces the immune response
CC (PubMed:30550790). Interacts with serine protease NS3 (By similarity).
CC Interacts with host KPNA2 (By similarity).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000250|UniProtKB:Q32ZE1,
CC ECO:0000269|PubMed:30550790, ECO:0000269|PubMed:30951555,
CC ECO:0000269|PubMed:32699085}.
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:P17763}; Multi-pass membrane protein
CC {ECO:0000255}. Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Envelope protein E]: Virion membrane
CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC {ECO:0000255}. Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 1]: Secreted
CC {ECO:0000250|UniProtKB:P17763}. Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q32ZE1}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q32ZE1}; 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:P17763}; Multi-pass membrane
CC protein {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:P17763}; 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 {ECO:0000250|UniProtKB:Q32ZE1};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q32ZE1}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:Q32ZE1}. Host nucleus
CC {ECO:0000269|PubMed:32699085}. Note=Located in RE-associated vesicles
CC hosting the replication complex. NS5 protein is mainly localized in the
CC nucleus rather than in ER vesicles. {ECO:0000250|UniProtKB:P17763}.
CC -!- DOMAIN: [Small envelope protein M]: The transmembrane domain contains
CC an endoplasmic reticulum retention signal.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- DOMAIN: [Envelope protein E]: The transmembrane domain contains an
CC endoplasmic reticulum retention signal. {ECO:0000250|UniProtKB:P17763}.
CC -!- DOMAIN: [Capsid protein C]: The disordered region at the N-terminus may
CC be involved in lipid-droplet binding. {ECO:0000250|UniProtKB:P12823}.
CC -!- DOMAIN: [Serine protease subunit NS2B]: The central disordered region
CC transitions to ordered by binding to NS3.
CC {ECO:0000250|UniProtKB:Q32ZE1}.
CC -!- DOMAIN: [RNA-directed RNA polymerase NS5]: Comprises a
CC methyltransferase (MTase) in the N-terminal region and an RNA-dependent
CC RNA polymerase in the C-terminal region.
CC {ECO:0000250|UniProtKB:Q32ZE1}.
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-glycosylation plays a role in virulence in
CC mammalian and mosquito hosts, but may have no effect on neurovirulence.
CC {ECO:0000269|PubMed:29091758}.
CC -!- PTM: [Envelope protein E]: Ubiquitination by host TRIM7 promotes virus
CC attachment and fusion of the virus and the host endosome membrane.
CC {ECO:0000250|UniProtKB:A0A142I5B9}.
CC -!- PTM: [Non-structural protein 1]: N-glycosylated. The excreted form is
CC glycosylated, which is required for efficient secretion of the protein
CC 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 -!- PTM: [RNA-directed RNA polymerase NS5]: Sumoylated, required for
CC regulating IFN induced interferon stimulated genes/ISGs.
CC {ECO:0000269|PubMed:32699085}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the class I-like SAM-
CC binding methyltransferase superfamily. mRNA cap 0-1 NS5-type
CC methyltransferase family. {ECO:0000255|PROSITE-ProRule:PRU00924}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Side effects - Issue 200 of
CC February 2018;
CC URL="https://web.expasy.org/spotlight/back_issues/200/";
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; KJ776791; AHZ13508.1; -; Genomic_RNA.
DR EMBL; KX447509; ANO46301.1; -; Genomic_RNA.
DR EMBL; KX447510; ANO46302.1; -; Genomic_RNA.
DR EMBL; KX447512; ANO46304.1; -; Genomic_RNA.
DR PDB; 5GOZ; X-ray; 2.05 A; A/B/C=2524-2785.
DR PDB; 5GP1; X-ray; 2.44 A; A/B/C=2524-2785.
DR PDB; 5H30; EM; 4.40 A; A/B/C=291-794, D/E/F=216-290.
DR PDB; 5H32; EM; 12.00 A; A/B/C=291-693.
DR PDB; 5H37; EM; 4.00 A; A/B/C=291-794, D/E/F=216-290.
DR PDB; 5IRE; EM; 3.80 A; A/C/E=291-794, B/D/F=216-290.
DR PDB; 5IZ7; EM; 3.70 A; A/B/C=291-794, D/E/F=216-290.
DR PDB; 5JMT; X-ray; 1.80 A; A=1674-2119.
DR PDB; 5KQR; X-ray; 1.33 A; A=2521-2786.
DR PDB; 5KQS; X-ray; 1.50 A; A=2521-2786.
DR PDB; 5KVE; X-ray; 1.70 A; E=588-697.
DR PDB; 5LBS; X-ray; 2.41 A; A/B=291-698.
DR PDB; 5LBV; X-ray; 2.20 A; A/B=291-698.
DR PDB; 5LCV; X-ray; 2.64 A; A/B=291-698.
DR PDB; 5M5B; X-ray; 2.01 A; A/B=2525-2786.
DR PDB; 5MRK; X-ray; 1.90 A; A/B=2521-2784.
DR PDB; 5NJU; X-ray; 2.10 A; A/B=2525-2784.
DR PDB; 5NJV; X-ray; 2.00 A; A/B/C/D=2524-2785.
DR PDB; 5U4W; EM; 9.10 A; G/I/K=726-791, H/J/L=238-290.
DR PDB; 5UHY; EM; 6.20 A; A/C/E=291-686.
DR PDB; 5ULP; X-ray; 1.55 A; A/B=2521-2788.
DR PDB; 5Y0A; EM; 22.00 A; A/B/C=291-693.
DR PDB; 5Y6M; X-ray; 2.00 A; A=1682-2119.
DR PDB; 5Y6N; X-ray; 1.57 A; A=1682-2119.
DR PDB; 6CO8; EM; 3.10 A; A/C/E=291-794, B/D/F=216-290.
DR PDB; 6I7P; X-ray; 3.98 A; A/B/C/D/E/F=2521-3423.
DR PDB; 6JFH; EM; 20.00 A; B/D/F=216-290.
DR PDB; 6JFI; EM; 11.00 A; B/D/F=216-290.
DR PDB; 6LD1; X-ray; 1.40 A; A=2790-3411.
DR PDB; 6LD2; X-ray; 1.40 A; A=2790-3411.
DR PDB; 6LD3; X-ray; 2.30 A; A=2790-3411.
DR PDB; 6LD4; X-ray; 1.50 A; A=2790-3411.
DR PDB; 6LD5; X-ray; 1.94 A; A=2790-3411.
DR PDB; 6NIP; X-ray; 4.16 A; E/Z=291-695.
DR PDB; 6NIU; X-ray; 4.30 A; A/B/E/Z=291-695.
DR PDB; 6PLK; X-ray; 2.30 A; E/F=588-697.
DR PDB; 6RWZ; X-ray; 1.70 A; A=1685-2125.
DR PDB; 6S0J; X-ray; 1.50 A; A=1685-2125.
DR PDB; 6UM3; X-ray; 2.50 A; A/B=1420-1466, A/B=1503-1684.
DR PDB; 7BSD; X-ray; 2.53 A; G/I=966-1146.
DR PDB; 7BU8; EM; 3.80 A; A/B/C=291-794.
DR PDB; 7BUA; EM; 4.80 A; A/B/C=291-794.
DR PDB; 7M1V; X-ray; 1.60 A; A/B=1420-1466, A/B=1504-1661.
DR PDBsum; 5GOZ; -.
DR PDBsum; 5GP1; -.
DR PDBsum; 5H30; -.
DR PDBsum; 5H32; -.
DR PDBsum; 5H37; -.
DR PDBsum; 5IRE; -.
DR PDBsum; 5IZ7; -.
DR PDBsum; 5JMT; -.
DR PDBsum; 5KQR; -.
DR PDBsum; 5KQS; -.
DR PDBsum; 5KVE; -.
DR PDBsum; 5LBS; -.
DR PDBsum; 5LBV; -.
DR PDBsum; 5LCV; -.
DR PDBsum; 5M5B; -.
DR PDBsum; 5MRK; -.
DR PDBsum; 5NJU; -.
DR PDBsum; 5NJV; -.
DR PDBsum; 5U4W; -.
DR PDBsum; 5UHY; -.
DR PDBsum; 5ULP; -.
DR PDBsum; 5Y0A; -.
DR PDBsum; 5Y6M; -.
DR PDBsum; 5Y6N; -.
DR PDBsum; 6CO8; -.
DR PDBsum; 6I7P; -.
DR PDBsum; 6JFH; -.
DR PDBsum; 6JFI; -.
DR PDBsum; 6LD1; -.
DR PDBsum; 6LD2; -.
DR PDBsum; 6LD3; -.
DR PDBsum; 6LD4; -.
DR PDBsum; 6LD5; -.
DR PDBsum; 6NIP; -.
DR PDBsum; 6NIU; -.
DR PDBsum; 6PLK; -.
DR PDBsum; 6RWZ; -.
DR PDBsum; 6S0J; -.
DR PDBsum; 6UM3; -.
DR PDBsum; 7BSD; -.
DR PDBsum; 7BU8; -.
DR PDBsum; 7BUA; -.
DR PDBsum; 7M1V; -.
DR SMR; A0A024B7W1; -.
DR IntAct; A0A024B7W1; 1.
DR BindingDB; A0A024B7W1; -.
DR iPTMnet; A0A024B7W1; -.
DR ABCD; A0A024B7W1; 12 sequenced antibodies.
DR BRENDA; 2.7.7.48; 9645.
DR BRENDA; 3.4.21.91; 9645.
DR Proteomes; UP000112691; Genome.
DR Proteomes; UP000137079; Genome.
DR Proteomes; UP000151151; Genome.
DR Proteomes; UP000168269; 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:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
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:0140272; F:exogenous protein binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004482; F:mRNA (guanine-N7-)-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039574; P:suppression by virus of host JAK-STAT cascade via inhibition of host TYK2 activity; IEA:UniProtKB-KW.
DR GO; GO: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:0039653; P:suppression by virus of host transcription; IDA:UniProtKB.
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 3D-structure; 4Fe-4S; Activation of host autophagy by virus; ATP-binding;
KW Capsid protein; Clathrin-mediated endocytosis of virus by host;
KW Cleavage on pair of basic residues; Disulfide bond;
KW Fusion of virus membrane with host endosomal membrane;
KW Fusion of virus membrane with host membrane; Glycoprotein; GTP-binding;
KW Helicase; Host cytoplasm; Host endoplasmic reticulum; Host membrane;
KW Host nucleus; Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host STAT1 by virus; Inhibition of host STAT2 by virus;
KW Inhibition of host TYK2 by virus; Iron; Iron-sulfur; Isopeptide bond;
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 Ubl conjugation; Viral attachment to host cell; Viral envelope protein;
KW Viral immunoevasion; Viral penetration into host cytoplasm;
KW Viral RNA replication; Virion; Virus endocytosis by host;
KW Virus entry into host cell; Zinc.
FT CHAIN 1..3423
FT /note="Genome polyprotein"
FT /id="PRO_0000443018"
FT CHAIN 1..104
FT /note="Capsid protein C"
FT /id="PRO_0000443019"
FT PROPEP 105..122
FT /note="ER anchor for capsid protein C, removed in mature
FT form by serine protease NS3"
FT /id="PRO_0000443020"
FT CHAIN 123..290
FT /note="Protein prM"
FT /id="PRO_0000443021"
FT CHAIN 123..215
FT /note="Peptide pr"
FT /id="PRO_0000443022"
FT CHAIN 216..290
FT /note="Small envelope protein M"
FT /id="PRO_0000443023"
FT CHAIN 291..794
FT /note="Envelope protein E"
FT /id="PRO_0000443024"
FT CHAIN 795..1146
FT /note="Non-structural protein 1"
FT /id="PRO_0000443025"
FT CHAIN 1147..1372
FT /note="Non-structural protein 2A"
FT /id="PRO_0000443026"
FT CHAIN 1373..1502
FT /note="Serine protease subunit NS2B"
FT /id="PRO_0000443027"
FT CHAIN 1503..2119
FT /note="Serine protease NS3"
FT /id="PRO_0000443028"
FT CHAIN 2120..2246
FT /note="Non-structural protein 4A"
FT /id="PRO_0000443029"
FT PEPTIDE 2247..2269
FT /note="Peptide 2k"
FT /id="PRO_0000443030"
FT CHAIN 2270..2520
FT /note="Non-structural protein 4B"
FT /id="PRO_0000443031"
FT CHAIN 2521..3423
FT /note="RNA-directed RNA polymerase NS5"
FT /id="PRO_0000443032"
FT TOPO_DOM 1..104
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 105..125
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 126..249
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 250..269
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 270..274
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 275..290
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 291..745
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 746..767
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 768..773
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 774..794
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 795..1177
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 1178..1198
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1199..1220
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1221..1241
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1242..1270
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 1271..1291
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1292..1295
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1296..1316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1317..1345
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 1346..1366
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1367..1373
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1374..1394
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1395..1397
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 1398..1418
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1419..1472
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 1473..1493
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1494..2170
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 2171..2191
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2192..2195
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT INTRAMEM 2196..2216
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2217..2218
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 2219..2239
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2240..2254
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT INTRAMEM 2255..2269
FT /note="Helical; Note=Signal for NS4B"
FT /evidence="ECO:0000305"
FT TOPO_DOM 2270..2307
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT INTRAMEM 2308..2328
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2329..2344
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 2345..2365
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2366..2375
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 2376..2396
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2397..2441
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 2442..2462
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2463..3423
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 1503..1680
FT /note="Peptidase S7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT DOMAIN 1683..1839
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 1834..2013
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 2521..2785
FT /note="mRNA cap 0-1 NS5-type MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT DOMAIN 3049..3199
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000250|UniProtKB:Q32ZE1"
FT REGION 37..72
FT /note="Hydrophobic; homodimerization of capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT REGION 388..401
FT /note="Fusion peptide"
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT REGION 1425..1464
FT /note="Interacts with and activates NS3 protease"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859"
FT REGION 1429..1451
FT /note="Disordered"
FT /evidence="ECO:0000250|UniProtKB:Q32ZE1"
FT REGION 1687..1690
FT /note="Important for RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P14340"
FT REGION 2597..2600
FT /note="SUMO-interacting motif (SIM)"
FT /evidence="ECO:0000269|PubMed:32699085"
FT MOTIF 1787..1790
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOTIF 2908..2914
FT /note="Nuclear localization signal (NLS)"
FT /evidence="ECO:0000250|UniProtKB:Q32ZE1"
FT ACT_SITE 1553
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1577
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1637
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 2581
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2666
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 1696..1703
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 2533..2539
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:27866982"
FT BINDING 2576
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924,
FT ECO:0000269|PubMed:27866982"
FT BINDING 2606
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924,
FT ECO:0000269|PubMed:27633330, ECO:0000269|PubMed:27866982,
FT ECO:0000269|PubMed:28031359"
FT BINDING 2607
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924,
FT ECO:0000269|PubMed:27633330, ECO:0000269|PubMed:27866982,
FT ECO:0000269|PubMed:28031359"
FT BINDING 2624
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924,
FT ECO:0000269|PubMed:27866982"
FT BINDING 2625
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924,
FT ECO:0000269|PubMed:27633330, ECO:0000269|PubMed:27866982,
FT ECO:0000269|PubMed:28031359"
FT BINDING 2630
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:27633330,
FT ECO:0000269|PubMed:27866982, ECO:0000269|PubMed:28031359"
FT BINDING 2631
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:27633330,
FT ECO:0000269|PubMed:27866982, ECO:0000269|PubMed:28031359"
FT BINDING 2651
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924,
FT ECO:0000269|PubMed:27633330, ECO:0000269|PubMed:27866982,
FT ECO:0000269|PubMed:28031359"
FT BINDING 2652
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924,
FT ECO:0000269|PubMed:27633330, ECO:0000269|PubMed:27866982,
FT ECO:0000269|PubMed:28031359"
FT BINDING 2666
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:27633330,
FT ECO:0000269|PubMed:27866982, ECO:0000269|PubMed:28031359"
FT BINDING 2667
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2669..2675
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:27866982"
FT BINDING 2733..2735
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:27866982"
FT BINDING 2740
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2959
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q32ZE1"
FT BINDING 2963
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q32ZE1"
FT BINDING 2968
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q32ZE1"
FT BINDING 2971
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q32ZE1"
FT BINDING 3234
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q32ZE1"
FT BINDING 3250
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q32ZE1"
FT BINDING 3369
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 104..105
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:Q32ZE1"
FT SITE 122..123
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:Q32ZE1"
FT SITE 139
FT /note="Fetal microcephaly"
FT SITE 215..216
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250|UniProtKB:Q32ZE1"
FT SITE 290..291
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 794..795
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1146..1147
FT /note="Cleavage; by host"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1372..1373
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1502..1503
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1958
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 1961
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 2119..2120
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2246..2247
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2269..2270
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2520..2521
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2533
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2536
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 2539
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2544
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2548
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2581
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2666
FT /note="Essential for 2'-O-methyltransferase and N-7
FT methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2670
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 2576
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 444
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000269|PubMed:27093288,
FT ECO:0000269|PubMed:27338953, ECO:0000269|PubMed:27882950,
FT ECO:0000269|PubMed:29091758"
FT CARBOHYD 924
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q32ZE1"
FT CARBOHYD 1001
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q32ZE1"
FT DISULFID 350..406
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 382..411
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 480..581
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 598..629
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 798..809
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 849..937
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 973..1017
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 1074..1123
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 1085..1106
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 1107..1110
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT CROSSLNK 328
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:A0A142I5B9"
FT CROSSLNK 571
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:A0A142I5B9"
FT MUTAGEN 444
FT /note="N->Q: Improves attachment, assembly and infectivity
FT in cell culture. Attenuates the virus in mouse and
FT mosquitoes."
FT /evidence="ECO:0000269|PubMed:29091758"
FT MUTAGEN 2545
FT /note="Y->A: Complete loss of dimer formation and about
FT three times increased polymerase activity; when associated
FT with S-2548 and A-2549."
FT /evidence="ECO:0000269|PubMed:30951555"
FT MUTAGEN 2548
FT /note="K->S: Complete loss of dimer formation and about
FT three times increased polymerase activity; when associated
FT with A-2545 and A-2549."
FT /evidence="ECO:0000269|PubMed:30951555"
FT MUTAGEN 2549
FT /note="K->A: Complete loss of dimer formation and about
FT three times increased polymerase activity; when associated
FT with A-2545 and S-2548."
FT /evidence="ECO:0000269|PubMed:30951555"
FT MUTAGEN 2772
FT /note="K->R: Loss of sumoylation and more than 80% loss of
FT binding to host STAT2."
FT /evidence="ECO:0000269|PubMed:32699085"
FT HELIX 222..225
FT /evidence="ECO:0007829|PDB:6CO8"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:6CO8"
FT TURN 237..241
FT /evidence="ECO:0007829|PDB:6CO8"
FT HELIX 243..253
FT /evidence="ECO:0007829|PDB:6CO8"
FT HELIX 257..264
FT /evidence="ECO:0007829|PDB:6CO8"
FT TURN 265..267
FT /evidence="ECO:0007829|PDB:6CO8"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:6CO8"
FT HELIX 274..285
FT /evidence="ECO:0007829|PDB:6CO8"
FT TURN 292..295
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 297..303
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 305..307
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 310..316
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 320..324
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:6CO8"
FT STRAND 331..340
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 345..362
FT /evidence="ECO:0007829|PDB:5LBV"
FT HELIX 373..376
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 380..390
FT /evidence="ECO:0007829|PDB:5LBV"
FT TURN 391..394
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 399..418
FT /evidence="ECO:0007829|PDB:5LBV"
FT HELIX 422..424
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 425..433
FT /evidence="ECO:0007829|PDB:5LBV"
FT HELIX 439..441
FT /evidence="ECO:0007829|PDB:5LBV"
FT TURN 448..450
FT /evidence="ECO:0007829|PDB:5LCV"
FT STRAND 454..460
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 461..463
FT /evidence="ECO:0007829|PDB:5LBS"
FT STRAND 465..469
FT /evidence="ECO:0007829|PDB:5LBV"
FT HELIX 471..473
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 474..481
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 483..486
FT /evidence="ECO:0007829|PDB:6CO8"
FT HELIX 488..490
FT /evidence="ECO:0007829|PDB:5LCV"
FT STRAND 491..496
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 499..504
FT /evidence="ECO:0007829|PDB:5LBV"
FT HELIX 505..509
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 515..517
FT /evidence="ECO:0007829|PDB:5LBV"
FT HELIX 529..532
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 533..537
FT /evidence="ECO:0007829|PDB:5LBV"
FT TURN 539..541
FT /evidence="ECO:0007829|PDB:5LBS"
FT STRAND 543..547
FT /evidence="ECO:0007829|PDB:5LBV"
FT HELIX 552..558
FT /evidence="ECO:0007829|PDB:5LBV"
FT TURN 559..561
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 562..568
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 571..573
FT /evidence="ECO:0007829|PDB:5LBV"
FT STRAND 578..584
FT /evidence="ECO:0007829|PDB:5LBV"
FT HELIX 585..587
FT /evidence="ECO:0007829|PDB:5LBS"
FT TURN 591..594
FT /evidence="ECO:0007829|PDB:5LCV"
FT STRAND 602..606
FT /evidence="ECO:0007829|PDB:5KVE"
FT STRAND 612..614
FT /evidence="ECO:0007829|PDB:6CO8"
FT STRAND 616..622
FT /evidence="ECO:0007829|PDB:5KVE"
FT STRAND 628..630
FT /evidence="ECO:0007829|PDB:5KVE"
FT STRAND 633..637
FT /evidence="ECO:0007829|PDB:5KVE"
FT TURN 639..641
FT /evidence="ECO:0007829|PDB:5KVE"
FT STRAND 644..648
FT /evidence="ECO:0007829|PDB:5KVE"
FT STRAND 650..652
FT /evidence="ECO:0007829|PDB:5KVE"
FT TURN 657..661
FT /evidence="ECO:0007829|PDB:6PLK"
FT STRAND 662..669
FT /evidence="ECO:0007829|PDB:5KVE"
FT STRAND 672..682
FT /evidence="ECO:0007829|PDB:5KVE"
FT STRAND 686..692
FT /evidence="ECO:0007829|PDB:5KVE"
FT HELIX 696..714
FT /evidence="ECO:0007829|PDB:6CO8"
FT HELIX 717..720
FT /evidence="ECO:0007829|PDB:6CO8"
FT STRAND 721..723
FT /evidence="ECO:0007829|PDB:6CO8"
FT HELIX 731..744
FT /evidence="ECO:0007829|PDB:6CO8"
FT TURN 745..747
FT /evidence="ECO:0007829|PDB:6CO8"
FT HELIX 752..767
FT /evidence="ECO:0007829|PDB:6CO8"
FT TURN 776..778
FT /evidence="ECO:0007829|PDB:6CO8"
FT HELIX 779..789
FT /evidence="ECO:0007829|PDB:6CO8"
FT STRAND 1068..1072
FT /evidence="ECO:0007829|PDB:7BSD"
FT STRAND 1078..1081
FT /evidence="ECO:0007829|PDB:7BSD"
FT STRAND 1093..1095
FT /evidence="ECO:0007829|PDB:7BSD"
FT STRAND 1104..1109
FT /evidence="ECO:0007829|PDB:7BSD"
FT STRAND 1115..1119
FT /evidence="ECO:0007829|PDB:7BSD"
FT STRAND 1122..1125
FT /evidence="ECO:0007829|PDB:7BSD"
FT STRAND 1422..1429
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1522..1531
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1534..1544
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1547..1550
FT /evidence="ECO:0007829|PDB:7M1V"
FT HELIX 1552..1555
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1560..1562
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1565..1567
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1569..1573
FT /evidence="ECO:0007829|PDB:7M1V"
FT TURN 1574..1577
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1578..1584
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1593..1595
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1597..1601
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1609..1613
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1616..1620
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1623..1627
FT /evidence="ECO:0007829|PDB:7M1V"
FT HELIX 1634..1636
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1640..1642
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1648..1651
FT /evidence="ECO:0007829|PDB:7M1V"
FT TURN 1652..1654
FT /evidence="ECO:0007829|PDB:7M1V"
FT STRAND 1678..1680
FT /evidence="ECO:0007829|PDB:5JMT"
FT HELIX 1685..1687
FT /evidence="ECO:0007829|PDB:5Y6N"
FT STRAND 1691..1694
FT /evidence="ECO:0007829|PDB:6S0J"
FT TURN 1702..1705
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 1706..1717
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1721..1727
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 1728..1737
FT /evidence="ECO:0007829|PDB:6S0J"
FT TURN 1738..1740
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1743..1745
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1760..1764
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 1765..1773
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1774..1776
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1782..1787
FT /evidence="ECO:0007829|PDB:6S0J"
FT TURN 1788..1790
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 1794..1808
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1813..1817
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1835..1839
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1848..1850
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 1852..1855
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1861..1864
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 1868..1880
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1885..1888
FT /evidence="ECO:0007829|PDB:6S0J"
FT TURN 1890..1892
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 1893..1902
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1906..1910
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 1912..1915
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1923..1927
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1930..1937
FT /evidence="ECO:0007829|PDB:6S0J"
FT TURN 1938..1940
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1941..1949
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 1952..1959
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 1971..1975
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 1983..1985
FT /evidence="ECO:0007829|PDB:5Y6N"
FT HELIX 1988..1996
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 2002..2004
FT /evidence="ECO:0007829|PDB:5Y6N"
FT HELIX 2011..2016
FT /evidence="ECO:0007829|PDB:6S0J"
FT TURN 2021..2024
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 2028..2039
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 2045..2053
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 2062..2064
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 2069..2071
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 2081..2083
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 2089..2091
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 2095..2098
FT /evidence="ECO:0007829|PDB:5Y6N"
FT HELIX 2099..2101
FT /evidence="ECO:0007829|PDB:6S0J"
FT STRAND 2102..2104
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 2105..2115
FT /evidence="ECO:0007829|PDB:6S0J"
FT HELIX 2528..2538
FT /evidence="ECO:0007829|PDB:5KQR"
FT HELIX 2541..2547
FT /evidence="ECO:0007829|PDB:5KQR"
FT TURN 2548..2551
FT /evidence="ECO:0007829|PDB:5KQR"
FT STRAND 2553..2556
FT /evidence="ECO:0007829|PDB:5KQR"
FT HELIX 2558..2565
FT /evidence="ECO:0007829|PDB:5KQR"
FT STRAND 2569..2571
FT /evidence="ECO:0007829|PDB:5NJV"
FT HELIX 2578..2587
FT /evidence="ECO:0007829|PDB:5KQR"
FT STRAND 2595..2600
FT /evidence="ECO:0007829|PDB:5KQR"
FT TURN 2603..2605
FT /evidence="ECO:0007829|PDB:5GP1"
FT HELIX 2606..2612
FT /evidence="ECO:0007829|PDB:5KQR"
FT STRAND 2617..2623
FT /evidence="ECO:0007829|PDB:5KQR"
FT HELIX 2641..2643
FT /evidence="ECO:0007829|PDB:5KQR"
FT STRAND 2644..2647
FT /evidence="ECO:0007829|PDB:5KQR"
FT HELIX 2652..2654
FT /evidence="ECO:0007829|PDB:5KQR"
FT STRAND 2661..2665
FT /evidence="ECO:0007829|PDB:5KQR"
FT HELIX 2674..2692
FT /evidence="ECO:0007829|PDB:5KQR"
FT STRAND 2697..2704
FT /evidence="ECO:0007829|PDB:5KQR"
FT HELIX 2709..2722
FT /evidence="ECO:0007829|PDB:5KQR"
FT STRAND 2725..2727
FT /evidence="ECO:0007829|PDB:5KQR"
FT STRAND 2739..2742
FT /evidence="ECO:0007829|PDB:5KQR"
FT HELIX 2749..2762
FT /evidence="ECO:0007829|PDB:5KQR"
FT STRAND 2765..2767
FT /evidence="ECO:0007829|PDB:5KQR"
FT STRAND 2772..2775
FT /evidence="ECO:0007829|PDB:5KQR"
FT HELIX 2795..2808
FT /evidence="ECO:0007829|PDB:6LD1"
FT TURN 2809..2812
FT /evidence="ECO:0007829|PDB:6LD1"
FT STRAND 2822..2832
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 2844..2848
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 2851..2855
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 2857..2860
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 2869..2878
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 2889..2906
FT /evidence="ECO:0007829|PDB:6LD1"
FT TURN 2907..2909
FT /evidence="ECO:0007829|PDB:6LD2"
FT HELIX 2917..2924
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 2943..2947
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 2950..2964
FT /evidence="ECO:0007829|PDB:6LD1"
FT STRAND 2973..2975
FT /evidence="ECO:0007829|PDB:6LD1"
FT STRAND 2996..2998
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3000..3010
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3012..3015
FT /evidence="ECO:0007829|PDB:6LD1"
FT TURN 3016..3019
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3021..3024
FT /evidence="ECO:0007829|PDB:6LD1"
FT STRAND 3025..3027
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3033..3044
FT /evidence="ECO:0007829|PDB:6LD1"
FT STRAND 3046..3049
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3059..3062
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3065..3071
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3072..3077
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3080..3093
FT /evidence="ECO:0007829|PDB:6LD1"
FT STRAND 3095..3104
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3106..3108
FT /evidence="ECO:0007829|PDB:6LD1"
FT STRAND 3110..3118
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3128..3147
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3154..3157
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3163..3178
FT /evidence="ECO:0007829|PDB:6LD1"
FT STRAND 3180..3183
FT /evidence="ECO:0007829|PDB:6LD1"
FT STRAND 3186..3189
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3194..3198
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3201..3205
FT /evidence="ECO:0007829|PDB:6LD1"
FT STRAND 3210..3213
FT /evidence="ECO:0007829|PDB:6LD3"
FT HELIX 3225..3227
FT /evidence="ECO:0007829|PDB:6LD1"
FT STRAND 3233..3239
FT /evidence="ECO:0007829|PDB:6LD1"
FT STRAND 3245..3250
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3253..3260
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3270..3287
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3292..3304
FT /evidence="ECO:0007829|PDB:6LD1"
FT STRAND 3326..3329
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3331..3339
FT /evidence="ECO:0007829|PDB:6LD1"
FT TURN 3340..3342
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3355..3357
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3363..3368
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3376..3383
FT /evidence="ECO:0007829|PDB:6LD1"
FT HELIX 3385..3396
FT /evidence="ECO:0007829|PDB:6LD1"
SQ SEQUENCE 3423 AA; 379113 MW; 5F0E490EE43DE346 CRC64;
MKNPKKKSGG FRIVNMLKRG VARVSPFGGL KRLPAGLLLG HGPIRMVLAI LAFLRFTAIK
PSLGLINRWG SVGKKEAMEI IKKFKKDLAA MLRIINARKE KKRRGADTSV GIVGLLLTTA
MAAEVTRRGS AYYMYLDRND AGEAISFPTT LGMNKCYIQI MDLGHMCDAT MSYECPMLDE
GVEPDDVDCW CNTTSTWVVY GTCHHKKGEA RRSRRAVTLP SHSTRKLQTR SQTWLESREY
TKHLIRVENW IFRNPGFALA AAAIAWLLGS STSQKVIYLV MILLIAPAYS IRCIGVSNRD
FVEGMSGGTW VDVVLEHGGC VTVMAQDKPT VDIELVTTTV SNMAEVRSYC YEASISDMAS
DSRCPTQGEA YLDKQSDTQY VCKRTLVDRG WGNGCGLFGK GSLVTCAKFA CSKKMTGKSI
QPENLEYRIM LSVHGSQHSG MIVNDTGHET DENRAKVEIT PNSPRAEATL GGFGSLGLDC
EPRTGLDFSD LYYLTMNNKH WLVHKEWFHD IPLPWHAGAD TGTPHWNNKE ALVEFKDAHA
KRQTVVVLGS QEGAVHTALA GALEAEMDGA KGRLSSGHLK CRLKMDKLRL KGVSYSLCTA
AFTFTKIPAE TLHGTVTVEV QYAGTDGPCK VPAQMAVDMQ TLTPVGRLIT ANPVITESTE
NSKMMLELDP PFGDSYIVIG VGEKKITHHW HRSGSTIGKA FEATVRGAKR MAVLGDTAWD
FGSVGGALNS LGKGIHQIFG AAFKSLFGGM SWFSQILIGT LLMWLGLNTK NGSISLMCLA
LGGVLIFLST AVSADVGCSV DFSKKETRCG TGVFVYNDVE AWRDRYKYHP DSPRRLAAAV
KQAWEDGICG ISSVSRMENI MWRSVEGELN AILEENGVQL TVVVGSVKNP MWRGPQRLPV
PVNELPHGWK AWGKSYFVRA AKTNNSFVVD GDTLKECPLK HRAWNSFLVE DHGFGVFHTS
VWLKVREDYS LECDPAVIGT AVKGKEAVHS DLGYWIESEK NDTWRLKRAH LIEMKTCEWP
KSHTLWTDGI EESDLIIPKS LAGPLSHHNT REGYRTQMKG PWHSEELEIR FEECPGTKVH
VEETCGTRGP SLRSTTASGR VIEEWCCREC TMPPLSFRAK DGCWYGMEIR PRKEPESNLV
RSMVTAGSTD HMDHFSLGVL VILLMVQEGL KKRMTTKIII STSMAVLVAM ILGGFSMSDL
AKLAILMGAT FAEMNTGGDV AHLALIAAFK VRPALLVSFI FRANWTPRES MLLALASCLL
QTAISALEGD LMVLINGFAL AWLAIRAMVV PRTDNITLAI LAALTPLARG TLLVAWRAGL
ATCGGFMLLS LKGKGSVKKN LPFVMALGLT AVRLVDPINV VGLLLLTRSG KRSWPPSEVL
TAVGLICALA GGFAKADIEM AGPMAAVGLL IVSYVVSGKS VDMYIERAGD ITWEKDAEVT
GNSPRLDVAL DESGDFSLVE DDGPPMREII LKVVLMTICG MNPIAIPFAA GAWYVYVKTG
KRSGALWDVP APKEVKKGET TDGVYRVMTR RLLGSTQVGV GVMQEGVFHT MWHVTKGSAL
RSGEGRLDPY WGDVKQDLVS YCGPWKLDAA WDGHSEVQLL AVPPGERARN IQTLPGIFKT
KDGDIGAVAL DYPAGTSGSP ILDKCGRVIG LYGNGVVIKN GSYVSAITQG RREEETPVEC
FEPSMLKKKQ LTVLDLHPGA GKTRRVLPEI VREAIKTRLR TVILAPTRVV AAEMEEALRG
LPVRYMTTAV NVTHSGTEIV DLMCHATFTS RLLQPIRVPN YNLYIMDEAH FTDPSSIAAR
GYISTRVEMG EAAAIFMTAT PPGTRDAFPD SNSPIMDTEV EVPERAWSSG FDWVTDHSGK
TVWFVPSVRN GNEIAACLTK AGKRVIQLSR KTFETEFQKT KHQEWDFVVT TDISEMGANF
KADRVIDSRR CLKPVILDGE RVILAGPMPV THASAAQRRG RIGRNPNKPG DEYLYGGGCA
ETDEDHAHWL EARMLLDNIY LQDGLIASLY RPEADKVAAI EGEFKLRTEQ RKTFVELMKR
GDLPVWLAYQ VASAGITYTD RRWCFDGTTN NTIMEDSVPA EVWTRHGEKR VLKPRWMDAR
VCSDHAALKS FKEFAAGKRG AAFGVMEALG TLPGHMTERF QEAIDNLAVL MRAETGSRPY
KAAAAQLPET LETIMLLGLL GTVSLGIFFV LMRNKGIGKM GFGMVTLGAS AWLMWLSEIE
PARIACVLIV VFLLLVVLIP EPEKQRSPQD NQMAIIIMVA VGLLGLITAN ELGWLERTKS
DLSHLMGRRE EGATIGFSMD IDLRPASAWA IYAALTTFIT PAVQHAVTTS YNNYSLMAMA
TQAGVLFGMG KGMPFYAWDF GVPLLMIGCY SQLTPLTLIV AIILLVAHYM YLIPGLQAAA
ARAAQKRTAA GIMKNPVVDG IVVTDIDTMT IDPQVEKKMG QVLLIAVAVS SAILSRTAWG
WGEAGALITA ATSTLWEGSP NKYWNSSTAT SLCNIFRGSY LAGASLIYTV TRNAGLVKRR
GGGTGETLGE KWKARLNQMS ALEFYSYKKS GITEVCREEA RRALKDGVAT GGHAVSRGSA
KLRWLVERGY LQPYGKVIDL GCGRGGWSYY AATIRKVQEV KGYTKGGPGH EEPMLVQSYG
WNIVRLKSGV DVFHMAAEPC DTLLCDIGES SSSPEVEEAR TLRVLSMVGD WLEKRPGAFC
IKVLCPYTST MMETLERLQR RYGGGLVRVP LSRNSTHEMY WVSGAKSNTI KSVSTTSQLL
LGRMDGPRRP VKYEEDVNLG SGTRAVVSCA EAPNMKIIGN RIERIRSEHA ETWFFDENHP
YRTWAYHGSY EAPTQGSASS LINGVVRLLS KPWDVVTGVT GIAMTDTTPY GQQRVFKEKV
DTRVPDPQEG TRQVMSMVSS WLWKELGKHK RPRVCTKEEF INKVRSNAAL GAIFEEEKEW
KTAVEAVNDP RFWALVDKER EHHLRGECQS CVYNMMGKRE KKQGEFGKAK GSRAIWYMWL
GARFLEFEAL GFLNEDHWMG RENSGGGVEG LGLQRLGYVL EEMSRIPGGR MYADDTAGWD
TRISRFDLEN EALITNQMEK GHRALALAII KYTYQNKVVK VLRPAEKGKT VMDIISRQDQ
RGSGQVVTYA LNTFTNLVVQ LIRNMEAEEV LEMQDLWLLR RSEKVTNWLQ SNGWDRLKRM
AVSGDDCVVK PIDDRFAHAL RFLNDMGKVR KDTQEWKPST GWDNWEEVPF CSHHFNKLHL
KDGRSIVVPC RHQDELIGRA RVSPGAGWSI RETACLAKSY AQMWQLLYFH RRDLRLMANA
ICSSVPVDWV PTGRTTWSIH GKGEWMTTED MLVVWNRVWI EENDHMEDKT PVTKWTDIPY
LGKREDLWCG SLIGHRPRTT WAENIKNTVN MVRRIIGDEE KYMDYLSTQV RYLGEEGSTP
GVL
