POLG_ZIKVK
ID POLG_ZIKVK Reviewed; 3423 AA.
AC A0A142I5B9; H9A910;
DT 07-NOV-2018, integrated into UniProtKB/Swiss-Prot.
DT 08-JUN-2016, sequence version 1.
DT 03-AUG-2022, entry version 38.
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:0000250|UniProtKB:P17763};
DE EC=2.1.1.56;
DE EC=2.1.1.57;
DE EC=2.7.7.48;
DE AltName: Full=NS5;
OS Zika virus (isolate ZIKV/Human/Cambodia/FSS13025/2010) (ZIKV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=2316109;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=22389730; DOI=10.1371/journal.pntd.0001477;
RA Haddow A.D., Schuh A.J., Yasuda C.Y., Kasper M.R., Heang V., Huy R.,
RA Guzman H., Tesh R.B., Weaver S.C.;
RT "Genetic characterization of zika virus strains: geographic expansion of
RT the asian lineage.";
RL PLoS Negl. Trop. Dis. 6:E1477-E1477(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=27174284; DOI=10.1128/genomea.00377-16;
RA Ladner J.T., Wiley M.R., Prieto K., Yasuda C.Y., Nagle E., Kasper M.R.,
RA Reyes D., Vasilakis N., Heang V., Weaver S.C., Haddow A., Tesh R.B.,
RA Sovann L., Palacios G.;
RT "Complete Genome Sequences of Five Zika Virus Isolates.";
RL Genome Announc. 4:0-0(2016).
RN [3]
RP MUTAGENESIS OF SER-139.
RX PubMed=28971967; DOI=10.1126/science.aam7120;
RA Yuan L., Huang X.Y., Liu Z.Y., Zhang F., Zhu X.L., Yu J.Y., Ji X., Xu Y.P.,
RA Li G., Li C., Wang H.J., Deng Y.Q., Wu M., Cheng M.L., Ye Q., Xie D.Y.,
RA Li X.F., Wang X., Shi W., Hu B., Shi P.Y., Xu Z., Qin C.F.;
RT "A single mutation in the prM protein of Zika virus contributes to fetal
RT microcephaly.";
RL Science 358:933-936(2017).
RN [4]
RP FUNCTION, MUTAGENESIS OF GLU-1249, INTERACTION WITH ENVELOPE PROTEIN E
RP (PROTEIN PRM), INTERACTION WITH ENVELOPE PROTEIN E (NON-STRUCTURAL PROTEIN
RP 2A), INTERACTION WITH SERINE PROTEASE SUBUNIT NS2B (NON-STRUCTURAL PROTEIN
RP 2A), INTERACTION WITH SERINE PROTEASE NS3 (NON-STRUCTURAL PROTEIN 2A),
RP INTERACTION NON-STRUCTURAL PROTEIN 2A (ENVELOPE PROTEIN E), INTERACTION
RP NON-STRUCTURAL PROTEIN 2A (SERINE PROTEASE SUBUNIT NS2B), INTERACTION
RP NON-STRUCTURAL PROTEIN 2A (SERINE PROTEASE NS3), AND INTERACTION
RP NON-STRUCTURAL PROTEIN 2A (PROTEIN PRM).
RX PubMed=31662457; DOI=10.1128/mbio.02375-19;
RA Zhang X., Xie X., Xia H., Zou J., Huang L., Popov V.L., Chen X., Shi P.Y.;
RT "Zika Virus NS2A-Mediated Virion Assembly.";
RL MBio 10:0-0(2019).
RN [5]
RP UBIQUITINATION (ENVELOPE PROTEIN E), FUNCTION (ENVELOPE PROTEIN E),
RP MUTAGENESIS OF LYS-328 AND LYS-571, AND INTERACTION WITH HOST HAVCR1
RP (ENVELOPE PROTEIN E).
RX PubMed=32641828; DOI=10.1038/s41586-020-2457-8;
RA Giraldo M.I., Xia H., Aguilera-Aguirre L., Hage A., van Tol S., Shan C.,
RA Xie X., Sturdevant G.L., Robertson S.J., McNally K.L., Meade-White K.,
RA Azar S.R., Rossi S.L., Maury W., Woodson M., Ramage H., Johnson J.R.,
RA Krogan N.J., Morais M.C., Best S.M., Shi P.Y., Rajsbaum R.;
RT "Envelope protein ubiquitination drives entry and pathogenesis of Zika
RT virus.";
RL Nature 585:414-419(2020).
RN [6]
RP FUNCTION (ENVELOPE PROTEIN E), AND INTERACTION WITH HOST NCAM1 (ENVELOPE
RP PROTEIN E).
RX PubMed=32753727; DOI=10.1038/s41467-020-17638-y;
RA Srivastava M., Zhang Y., Chen J., Sirohi D., Miller A., Zhang Y., Chen Z.,
RA Lu H., Xu J., Kuhn R.J., Andy Tao W.;
RT "Chemical proteomics tracks virus entry and uncovers NCAM1 as Zika virus
RT receptor.";
RL Nat. Commun. 11:3896-3896(2020).
RN [7]
RP FUNCTION (ENVELOPE PROTEIN E), INTERACTION WITH HOST HSPA5 (ENVELOPE
RP PROTEIN E), AND SUBCELLULAR LOCATION (ENVELOPE PROTEIN E).
RX PubMed=33432092; DOI=10.1038/s41598-020-79803-z;
RA Khongwichit S., Sornjai W., Jitobaom K., Greenwood M., Greenwood M.P.,
RA Hitakarun A., Wikan N., Murphy D., Smith D.R.;
RT "A functional interaction between GRP78 and Zika virus E protein.";
RL Sci. Rep. 11:393-393(2021).
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 (PubMed:32641828). In addition, host
CC NCAM1 can also be used as entry receptor (PubMed:32753727). Interaction
CC with host HSPA5 plays an important role in the early stages of
CC infection as well (PubMed:33432092). Envelope protein is synthesized in
CC the 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:P17763,
CC ECO:0000269|PubMed:32641828, ECO:0000269|PubMed:32753727,
CC ECO:0000269|PubMed:33432092}.
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 (PubMed:31662457).
CC Antagonizes also the host alpha/beta interferon antiviral response (By
CC similarity). May disrupt adherens junction formation and thereby impair
CC proliferation of radial cells in the host cortex (By similarity).
CC {ECO:0000250|UniProtKB:Q32ZE1, ECO:0000269|PubMed:31662457}.
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 (By similarity).
CC {ECO:0000250|UniProtKB:A0A024B7W1, ECO:0000250|UniProtKB:Q32ZE1}.
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 (By similarity). By inhibiting host ANKLE2 functions, may
CC cause defects in brain development, such as microcephaly (By
CC similarity). 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 (By similarity).
CC {ECO:0000250|UniProtKB:A0A024B7W1, ECO:0000250|UniProtKB:Q32ZE1,
CC 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 (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 (By similarity).
CC {ECO:0000250|UniProtKB:Q32ZE1, 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 (By similarity). Methylates viral RNA cap at guanine N-7 and
CC ribose 2'-O positions. Once sufficient NS5 is expressed, binds to the
CC cap-proximal structure and inhibits further translation of the viral
CC genome (By similarity). Besides its role in RNA genome replication,
CC also prevents the establishment of a cellular antiviral state by
CC blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway.
CC Mechanistically, interferes with host kinases TBK1 and IKKE upstream of
CC interferon regulatory factor 3/IRF3 to inhibit the RIG-I pathway (By
CC similarity). Antagonizes also type I interferon signaling by targeting
CC STAT2 for degradation by the proteasome thereby preventing activation
CC of JAK-STAT signaling pathway (By similarity). Within the host nucleus,
CC disrupts host SUMO1 and STAT2 co-localization with PML, resulting in
CC PML degradation (By similarity). May also reduce immune responses by
CC preventing the recruitment of the host PAF1 complex to interferon-
CC responsive genes (By similarity). {ECO:0000250|UniProtKB:A0A024B7W1,
CC ECO:0000250|UniProtKB:Q32ZE1}.
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 -!- 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. {ECO:0000250|UniProtKB:P17763,
CC ECO:0000269|PubMed:31662457}.
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 (By similarity). Interacts with non-structural protein 2A
CC (PubMed:31662457). Interacts with host HAVCR1; this interaction likely
CC mediates virus attachment to host cell (PubMed:32641828). Interacts
CC with host NCAM1 (PubMed:32753727). Interacts with host HSPA5
CC (PubMed:33432092). {ECO:0000250|UniProtKB:A0A024B7W1,
CC ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:31662457,
CC ECO:0000269|PubMed:32641828, ECO:0000269|PubMed:32753727,
CC ECO:0000269|PubMed:33432092}.
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:0000269|PubMed:31662457}.
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 (PubMed:31662457).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000250|UniProtKB:Q32ZE1,
CC ECO:0000269|PubMed:31662457}.
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
CC (PubMed:31662457). Interacts with host SHFL; this interaction promotes
CC NS3 degradation via a lysosome-dependent pathway (By similarity).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000250|UniProtKB:Q32ZE1,
CC ECO:0000269|PubMed:31662457}.
CC -!- SUBUNIT: [Non-structural protein 4A]: May interact with host ANKLE2;
CC the interaction may cause defects in brain development, such as
CC microcephaly (By similarity). May interact with host SRPRA and SEC61G
CC (By similarity). {ECO:0000250|UniProtKB:A0A024B7W1}.
CC -!- SUBUNIT: [Non-structural protein 4B]: Interacts with serine protease
CC NS3 (By similarity). Interacts with NS1 (By similarity).
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase NS5]: Homodimer (By similarity).
CC Interacts with host STAT2; this interaction inhibits the
CC phosphorylation of the latter, and, when all viral proteins are present
CC (polyprotein), targets STAT2 for degradation (By similarity). Interacts
CC with host TBK1 and IKBKE; these interactions lead to the inhibition of
CC the host RIG-I signaling pathway (By similarity). Interacts with host
CC PAF1 complex; the interaction may prevent the recruitment of the host
CC PAF1 complex to interferon-responsive genes, and thus reduces the
CC immune response (By similarity). Interacts with serine protease NS3 (By
CC similarity). Interacts with host KPNA2 (By similarity).
CC {ECO:0000250|UniProtKB:A0A024B7W1, ECO:0000250|UniProtKB:P17763,
CC ECO:0000250|UniProtKB:Q32ZE1}.
CC -!- INTERACTION:
CC A0A142I5B9; Q8N111: CEND1; Xeno; NbExp=3; IntAct=EBI-20625235, EBI-946825;
CC A0A142I5B9; Q99653: CHP1; Xeno; NbExp=2; IntAct=EBI-20625235, EBI-722721;
CC A0A142I5B9; Q9NWW5: CLN6; Xeno; NbExp=4; IntAct=EBI-20625235, EBI-6165897;
CC A0A142I5B9; Q4G0J3: LARP7; Xeno; NbExp=2; IntAct=EBI-20625235, EBI-2371923;
CC A0A142I5B9; Q9NX58: LYAR; Xeno; NbExp=2; IntAct=EBI-20625235, EBI-713507;
CC A0A142I5B9; Q8NEJ9: NGDN; Xeno; NbExp=2; IntAct=EBI-20625235, EBI-9995414;
CC A0A142I5B9; O43251-6: RBFOX2; Xeno; NbExp=3; IntAct=EBI-20625235, EBI-10987522;
CC A0A142I5B9; O00767: SCD; Xeno; NbExp=3; IntAct=EBI-20625235, EBI-2684237;
CC A0A142I5B9; Q16637: SMN2; Xeno; NbExp=2; IntAct=EBI-20625235, EBI-395421;
CC A0A142I5B9; Q5BJD5: TMEM41B; Xeno; NbExp=3; IntAct=EBI-20625235, EBI-1055840;
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}. Host cell surface {ECO:0000269|PubMed:33432092}.
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:0000250|UniProtKB:P17763}. 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:A0A024B7W1}.
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:0000250|UniProtKB:A0A024B7W1}.
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:0000269|PubMed:32641828}.
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:0000250|UniProtKB:A0A024B7W1}.
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; JN860885; AFD30972.1; -; Genomic_RNA.
DR EMBL; KU955593; AMR39834.1; -; Genomic_RNA.
DR PDB; 6UTA; X-ray; 3.10 A; C/E=588-697.
DR PDB; 7BPK; X-ray; 3.10 A; A/B=291-699.
DR PDB; 7BQ5; X-ray; 2.99 A; A/B=291-699.
DR PDBsum; 6UTA; -.
DR PDBsum; 7BPK; -.
DR PDBsum; 7BQ5; -.
DR SMR; A0A142I5B9; -.
DR IntAct; A0A142I5B9; 385.
DR Proteomes; UP000157401; 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:0044228; C:host cell surface; 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: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: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: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 CDD; cd12149; Flavi_E_C; 1.
DR Gene3D; 1.10.10.930; -; 1.
DR Gene3D; 1.10.8.970; -; 1.
DR Gene3D; 1.20.1280.260; -; 1.
DR Gene3D; 2.60.260.50; -; 1.
DR Gene3D; 2.60.40.350; -; 1.
DR Gene3D; 2.60.98.10; -; 1.
DR Gene3D; 3.30.387.10; -; 1.
DR Gene3D; 3.30.67.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR011492; DEAD_Flavivir.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR000069; Env_glycoprot_M_flavivir.
DR InterPro; IPR038302; Env_glycoprot_M_sf_flavivir.
DR InterPro; IPR013755; Flav_gly_cen_dom_subdom1.
DR InterPro; IPR001122; Flavi_capsidC.
DR InterPro; IPR037172; Flavi_capsidC_sf.
DR InterPro; IPR027287; Flavi_E_Ig-like.
DR InterPro; IPR026470; Flavi_E_Stem/Anchor_dom.
DR InterPro; IPR038345; Flavi_E_Stem/Anchor_dom_sf.
DR InterPro; IPR001157; Flavi_NS1.
DR InterPro; IPR000752; Flavi_NS2A.
DR InterPro; IPR000487; Flavi_NS2B.
DR InterPro; IPR000404; Flavi_NS4A.
DR InterPro; IPR001528; Flavi_NS4B.
DR InterPro; IPR002535; Flavi_propep.
DR InterPro; IPR038688; Flavi_propep_sf.
DR InterPro; IPR000336; Flavivir/Alphavir_Ig-like_sf.
DR InterPro; IPR001850; Flavivirus_NS3_S7.
DR InterPro; IPR014412; Gen_Poly_FLV.
DR InterPro; IPR011998; Glycoprot_cen/dimer.
DR InterPro; IPR036253; Glycoprot_cen/dimer_sf.
DR InterPro; IPR038055; Glycoprot_E_dimer_dom.
DR InterPro; IPR013756; GlyE_cen_dom_subdom2.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR026490; mRNA_cap_0/1_MeTrfase.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR000208; RNA-dir_pol_flavivirus.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR InterPro; IPR002877; RNA_MeTrfase_FtsJ_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF01003; Flavi_capsid; 1.
DR Pfam; PF07652; Flavi_DEAD; 1.
DR Pfam; PF02832; Flavi_glycop_C; 1.
DR Pfam; PF00869; Flavi_glycoprot; 1.
DR Pfam; PF01004; Flavi_M; 1.
DR Pfam; PF00948; Flavi_NS1; 1.
DR Pfam; PF01005; Flavi_NS2A; 1.
DR Pfam; PF01002; Flavi_NS2B; 1.
DR Pfam; PF01350; Flavi_NS4A; 1.
DR Pfam; PF01349; Flavi_NS4B; 1.
DR Pfam; PF00972; Flavi_NS5; 1.
DR Pfam; PF01570; Flavi_propep; 1.
DR Pfam; PF01728; FtsJ; 1.
DR Pfam; PF00949; Peptidase_S7; 1.
DR PIRSF; PIRSF003817; Gen_Poly_FLV; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF101257; SSF101257; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR SUPFAM; SSF56983; SSF56983; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR TIGRFAMs; TIGR04240; flavi_E_stem; 1.
DR PROSITE; PS51527; FLAVIVIRUS_NS2B; 1.
DR PROSITE; PS51528; FLAVIVIRUS_NS3PRO; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR PROSITE; PS51591; RNA_CAP01_NS5_MT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activation of host autophagy by virus; ATP-binding;
KW Capsid protein; 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 STAT2 by virus; Isopeptide bond; Membrane;
KW 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; Transferase; Transmembrane; Transmembrane helix;
KW Ubl conjugation; Viral attachment to host cell; Viral immunoevasion;
KW Viral penetration into host cytoplasm; Viral RNA replication; Virion;
KW Virus entry into host cell; Zinc.
FT CHAIN 1..3423
FT /note="Genome polyprotein"
FT /id="PRO_0000445659"
FT CHAIN 1..104
FT /note="Capsid protein C"
FT /id="PRO_0000445660"
FT PROPEP 105..122
FT /note="ER anchor for capsid protein C, removed in mature
FT form by serine protease NS3"
FT /id="PRO_0000445661"
FT CHAIN 123..290
FT /note="Protein prM"
FT /id="PRO_0000445662"
FT CHAIN 123..215
FT /note="Peptide pr"
FT /id="PRO_0000445663"
FT CHAIN 216..290
FT /note="Small envelope protein M"
FT /id="PRO_0000445664"
FT CHAIN 291..794
FT /note="Envelope protein E"
FT /id="PRO_0000445665"
FT CHAIN 795..1146
FT /note="Non-structural protein 1"
FT /id="PRO_0000445666"
FT CHAIN 1147..1372
FT /note="Non-structural protein 2A"
FT /id="PRO_0000445667"
FT CHAIN 1373..1502
FT /note="Serine protease subunit NS2B"
FT /id="PRO_0000445668"
FT CHAIN 1503..2119
FT /note="Serine protease NS3"
FT /id="PRO_0000445669"
FT CHAIN 2120..2246
FT /note="Non-structural protein 4A"
FT /id="PRO_0000445670"
FT PEPTIDE 2247..2269
FT /note="Peptide 2k"
FT /id="PRO_0000445671"
FT CHAIN 2270..2520
FT /note="Non-structural protein 4B"
FT /id="PRO_0000445672"
FT CHAIN 2521..3423
FT /note="RNA-directed RNA polymerase NS5"
FT /id="PRO_0000445673"
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:0000250|UniProtKB:A0A024B7W1"
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:0000250|UniProtKB:A0A024B7W1"
FT BINDING 2576
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2606
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2607
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2624
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2625
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2630
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A0A024B7W1"
FT BINDING 2631
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A0A024B7W1"
FT BINDING 2651
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2652
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2666
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A0A024B7W1"
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:0000250|UniProtKB:A0A024B7W1"
FT BINDING 2733..2735
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:A0A024B7W1"
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 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:0000250|UniProtKB:A0A024B7W1"
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:0000269|PubMed:32641828"
FT CROSSLNK 571
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:32641828"
FT MUTAGEN 139
FT /note="S->N: Increased viral infectivity."
FT /evidence="ECO:0000269|PubMed:28971967"
FT MUTAGEN 328
FT /note="K->R: Complete loss of binding to host HAVCR1."
FT /evidence="ECO:0000269|PubMed:32641828"
FT MUTAGEN 571
FT /note="K->R: Reduced ubiquitination of Envelope protein E."
FT /evidence="ECO:0000269|PubMed:32641828"
FT MUTAGEN 1249
FT /note="E->A: Complete loss of virus production by impairing
FT NS2A binding to prM/E and NS2B/NS3."
FT /evidence="ECO:0000269|PubMed:31662457"
FT STRAND 600..604
FT /evidence="ECO:0007829|PDB:6UTA"
FT STRAND 615..623
FT /evidence="ECO:0007829|PDB:6UTA"
FT STRAND 633..636
FT /evidence="ECO:0007829|PDB:6UTA"
FT STRAND 638..640
FT /evidence="ECO:0007829|PDB:6UTA"
FT STRAND 650..652
FT /evidence="ECO:0007829|PDB:6UTA"
FT STRAND 657..661
FT /evidence="ECO:0007829|PDB:6UTA"
FT STRAND 663..668
FT /evidence="ECO:0007829|PDB:6UTA"
FT STRAND 672..679
FT /evidence="ECO:0007829|PDB:6UTA"
FT STRAND 681..684
FT /evidence="ECO:0007829|PDB:6UTA"
FT STRAND 690..692
FT /evidence="ECO:0007829|PDB:6UTA"
SQ SEQUENCE 3423 AA; 379109 MW; 121FD6A9B721A7B3 CRC64;
MKNPKKKSGG FRIVNMLKRG VARVSPFGGL KRLPAGLLLG HGPIRMVLAI LAFLRFTAIK
PSLGLINRWG SVGKKEAMEI IKKFKKDLAA MLRIINARKE KKRRGTDTSV GIVGLLLTTA
MAVEVTRRGN AYYMYLDRSD AGEAISFPTT MGMNKCYIQI 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 LLVWLGLNTK NGSISLMCLA
LGGVLIFLST AVSADVGCSV DFSKKETRCG TGVFVYNDVE AWRDRYKYHP DSPRRLAAAV
KQAWEDGICG ISSVSRMENI MWRSVEGELN AILEENGVQL TVVVGSVKNP MWRGPQRLPV
PVNELPHGWK AWGKSYFVRA AKTNNSFVVD GDTLKECPLK HRAWNSFLVE DHGFGVFHTS
VWLKVREDYS LECDPAVIGT AAKGKEAVHS 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 LMVPINGFAL AWLAIRAMVV PRTDNITLAI LAALTPLARG TLLVAWRAGL
ATCGGFMLLS LKGKGSVKKN LPFVMALGLT AVRLVDPINV VGLLLLTRSG KRSWPPSEVL
TAVGLICALA GGFAKADIEM AGPMAAVGLL IVSYVVSGKS VDMYIERAGD ITWEKDAEVT
GNSPRLDVAL DESGDFSLVE DDGPPMREII LKVVLMAICG 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 EVWTRYGEKR 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 MMRRIIGDEE KYVDYLSTQV RYLGEEGSTP
GVL
