POLN_CHIKS
ID POLN_CHIKS Reviewed; 2474 AA.
AC Q8JUX6;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Polyprotein P1234;
DE Short=P1234;
DE AltName: Full=Non-structural polyprotein;
DE Contains:
DE RecName: Full=Polyprotein P123;
DE Short=P123;
DE Contains:
DE RecName: Full=mRNA-capping enzyme nsP1;
DE EC=2.1.1.- {ECO:0000250|UniProtKB:P27282};
DE EC=2.7.7.- {ECO:0000250|UniProtKB:P27282};
DE AltName: Full=Non-structural protein 1;
DE Contains:
DE RecName: Full=Protease nsP2;
DE EC=3.1.3.33 {ECO:0000269|PubMed:21811589};
DE EC=3.4.22.- {ECO:0000269|PubMed:26597768, ECO:0000269|PubMed:27845418};
DE EC=3.6.1.15 {ECO:0000269|PubMed:21811589, ECO:0000269|PubMed:24407286};
DE EC=3.6.4.13 {ECO:0000269|PubMed:21811589, ECO:0000269|PubMed:24407286};
DE AltName: Full=Non-structural protein 2;
DE Short=nsP2;
DE Contains:
DE RecName: Full=Non-structural protein 3;
DE Short=nsP3;
DE EC=3.1.3.84 {ECO:0000269|PubMed:19386706};
DE Contains:
DE RecName: Full=RNA-directed RNA polymerase nsP4;
DE EC=2.7.7.19 {ECO:0000250|UniProtKB:P03317};
DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
DE AltName: Full=Non-structural protein 4;
DE Short=nsP4;
OS Chikungunya virus (strain S27-African prototype) (CHIKV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Martellivirales; Togaviridae; Alphavirus.
OX NCBI_TaxID=371094;
OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OH NCBI_TaxID=7160; Aedes albopictus (Asian tiger mosquito) (Stegomyia albopicta).
OH NCBI_TaxID=299627; Aedes furcifer (Mosquito).
OH NCBI_TaxID=188700; Aedes polynesiensis (Polynesian tiger mosquito).
OH NCBI_TaxID=9533; Cercopithecus.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9539; Macaca (macaques).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
OH NCBI_TaxID=9554; Papio (baboons).
OH NCBI_TaxID=9573; Presbytis.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=12466484; DOI=10.1099/0022-1317-83-12-3075;
RA Khan A.H., Morita K., Parquet Md Mdel C., Hasebe F., Mathenge E.G.,
RA Igarashi A.;
RT "Complete nucleotide sequence of chikungunya virus and evidence for an
RT internal polyadenylation site.";
RL J. Gen. Virol. 83:3075-3084(2002).
RN [2]
RP FUNCTION (PROTEASE NSP2), CATALYTIC ACTIVITY (PROTEASE NSP2), COFACTOR
RP (PROTEASE NSP2), BIOPHYSICOCHEMICAL PROPERTIES (PROTEASE NSP2), AND
RP MUTAGENESIS OF LYS-727 AND 787-ASP-GLU-788.
RC STRAIN=Andhra Pradesh;
RX PubMed=21811589; DOI=10.1371/journal.pone.0022336;
RA Karpe Y.A., Aher P.P., Lole K.S.;
RT "NTPase and 5'-RNA triphosphatase activities of Chikungunya virus nsP2
RT protein.";
RL PLoS ONE 6:E22336-E22336(2011).
RN [3]
RP FUNCTION (PROTEASE NSP2).
RX PubMed=22514352; DOI=10.1128/jvi.00541-12;
RA Akhrymuk I., Kulemzin S.V., Frolova E.I.;
RT "Evasion of the innate immune response: the Old World alphavirus nsP2
RT protein induces rapid degradation of Rpb1, a catalytic subunit of RNA
RT polymerase II.";
RL J. Virol. 86:7180-7191(2012).
RN [4]
RP INTERACTION WITH MRNA-CAPPING ENZYME NSP1 (NON-STRUCTURAL PROTEIN 3),
RP INTERACTION WITH NON-STRUCTURAL PROTEIN 3 (INTERACTION WITH MRNA-CAPPING
RP ENZYME NSP1), INTERACTION WITH MRNA-CAPPING ENZYME NSP1 (RNA-DIRECTED RNA
RP POLYMERASE NSP4), INTERACTION WITH RNA-DIRECTED RNA POLYMERASE NSP4
RP (MRNA-CAPPING ENZYME NSP1), INTERACTION WITH RNA-DIRECTED RNA POLYMERASE
RP NSP4 (NON-STRUCTURAL PROTEIN 2), INTERACTION WITH NON-STRUCTURAL PROTEIN 2
RP (RNA-DIRECTED RNA POLYMERASE NSP4), INTERACTION WITH MRNA-CAPPING ENZYME
RP NSP1 (NON-STRUCTURAL PROTEIN 2), AND INTERACTION WITH NON-STRUCTURAL
RP PROTEIN 2 (MRNA-CAPPING ENZYME NSP1).
RX PubMed=22951312; DOI=10.1016/j.virusres.2012.08.006;
RA Sreejith R., Rana J., Dudha N., Kumar K., Gabrani R., Sharma S.K.,
RA Gupta A., Vrati S., Chaudhary V.K., Gupta S.;
RT "Mapping interactions of Chikungunya virus nonstructural proteins.";
RL Virus Res. 169:231-236(2012).
RN [5]
RP DOMAIN (PROTEASE NSP2), CATALYTIC ACTIVITY (PROTEASE NSP2), COFACTOR
RP (PROTEASE NSP2), BIOPHYSICOCHEMICAL PROPERTIES (PROTEASE NSP2), AND
RP FUNCTION (PROTEASE NSP2).
RX PubMed=24407286; DOI=10.1074/jbc.m113.503433;
RA Das P.K., Merits A., Lulla A.;
RT "Functional cross-talk between distant domains of chikungunya virus non-
RT structural protein 2 is decisive for its RNA-modulating activity.";
RL J. Biol. Chem. 289:5635-5653(2014).
RN [6]
RP DOMAIN (NON-STRUCTURAL PROTEIN 3), AND INTERACTION WITH HOST G3BP1
RP (NON-STRUCTURAL PROTEIN 3).
RX PubMed=24623412; DOI=10.1128/jvi.00439-14;
RA Panas M.D., Ahola T., McInerney G.M.;
RT "The C-terminal repeat domains of nsP3 from the Old World alphaviruses bind
RT directly to G3BP.";
RL J. Virol. 88:5888-5893(2014).
RN [7]
RP FUNCTION (PROTEASE NSP2), MUTAGENESIS OF CYS-1013; SER-1017 AND TRP-1084,
RP AND CATALYTIC ACTIVITY (PROTEASE NSP2).
RX PubMed=26597768; DOI=10.1038/srep17125;
RA Saisawang C., Saitornuang S., Sillapee P., Ubol S., Smith D.R.,
RA Ketterman A.J.;
RT "Chikungunya nsP2 protease is not a papain-like cysteine protease and the
RT catalytic dyad cysteine is interchangeable with a proximal serine.";
RL Sci. Rep. 5:17125-17125(2015).
RN [8]
RP FUNCTION (NON-STRUCTURAL PROTEIN 3).
RX PubMed=25653451; DOI=10.1128/jvi.03612-14;
RA Scholte F.E., Tas A., Albulescu I.C., Zusinaite E., Merits A.,
RA Snijder E.J., van Hemert M.J.;
RT "Stress granule components G3BP1 and G3BP2 play a proviral role early in
RT Chikungunya virus replication.";
RL J. Virol. 89:4457-4469(2015).
RN [9]
RP INTERACTION WITH HOST G3BP1 (NON-STRUCTURAL PROTEIN 3), MUTAGENESIS OF
RP PHE-1812 AND PHE-1830, DOMAIN (NON-STRUCTURAL PROTEIN 3), AND FUNCTION
RP (NON-STRUCTURAL PROTEIN 3).
RX PubMed=27383630; DOI=10.1098/rsob.160078;
RA Schulte T., Liu L., Panas M.D., Thaa B., Dickson N., Gotte B., Achour A.,
RA McInerney G.M.;
RT "Combined structural, biochemical and cellular evidence demonstrates that
RT both FGDF motifs in alphavirus nsP3 are required for efficient
RT replication.";
RL Open Biol. 6:0-0(2016).
RN [10]
RP CATALYTIC ACTIVITY (PROTEASE NSP2), FUNCTION (PROTEASE NSP2), ACTIVE SITE
RP (PROTEASE NSP2), PROTEOLYTIC CLEAVAGE (POLYPROTEIN P1234), FUNCTION
RP (POLYPROTEIN P1234), AND MUTAGENESIS OF CYS-1013; TRP-1014 AND SER-1017.
RX PubMed=27845418; DOI=10.1038/srep37124;
RA Rausalu K., Utt A., Quirin T., Varghese F.S., Zusinaite E., Das P.K.,
RA Ahola T., Merits A.;
RT "Chikungunya virus infectivity, RNA replication and non-structural
RT polyprotein processing depend on the nsP2 protease's active site cysteine
RT residue.";
RL Sci. Rep. 6:37124-37124(2016).
RN [11]
RP FUNCTION (NON-STRUCTURAL PROTEIN 3), INTERACTION WITH HOST G3BP1
RP (NON-STRUCTURAL PROTEIN 3), AND DOMAIN (NON-STRUCTURAL PROTEIN 3).
RX PubMed=27509095; DOI=10.1371/journal.ppat.1005810;
RA Kim D.Y., Reynaud J.M., Rasalouskaya A., Akhrymuk I., Mobley J.A.,
RA Frolov I., Frolova E.I.;
RT "New World and Old World Alphaviruses Have Evolved to Exploit Different
RT Components of Stress Granules, FXR and G3BP Proteins, for Assembly of Viral
RT Replication Complexes.";
RL PLoS Pathog. 12:E1005810-E1005810(2016).
RN [12]
RP FUNCTION (NON-STRUCTURAL PROTEIN 3), DOMAIN (NON-STRUCTURAL PROTEIN 3), AND
RP CATALYTIC ACTIVITY (NON-STRUCTURAL PROTEIN 3).
RX PubMed=28143925; DOI=10.1073/pnas.1621485114;
RA McPherson R.L., Abraham R., Sreekumar E., Ong S.E., Cheng S.J.,
RA Baxter V.K., Kistemaker H.A., Filippov D.V., Griffin D.E., Leung A.K.;
RT "ADP-ribosylhydrolase activity of Chikungunya virus macrodomain is critical
RT for virus replication and virulence.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:1666-1671(2017).
RN [13]
RP FUNCTION (NON-STRUCTURAL PROTEIN 3), DOMAIN (NON-STRUCTURAL PROTEIN 3),
RP MUTAGENESIS OF ASN-1357; VAL-1366 AND TYR-1447, AND CATALYTIC ACTIVITY
RP (NON-STRUCTURAL PROTEIN 3).
RX PubMed=28150709; DOI=10.1038/srep41746;
RA Eckei L., Krieg S., Buetepage M., Lehmann A., Gross A., Lippok B.,
RA Grimm A.R., Kuemmerer B.M., Rossetti G., Luescher B., Verheugd P.;
RT "The conserved macrodomains of the non-structural proteins of Chikungunya
RT virus and other pathogenic positive strand RNA viruses function as mono-
RT ADP-ribosylhydrolases.";
RL Sci. Rep. 7:41746-41746(2017).
RN [14]
RP READTHROUGH.
RX PubMed=29138302; DOI=10.1128/mbio.01456-17;
RA Jones J.E., Long K.M., Whitmore A.C., Sanders W., Thurlow L.R., Brown J.A.,
RA Morrison C.R., Vincent H., Peck K.M., Browning C., Moorman N., Lim J.K.,
RA Heise M.T.;
RT "Disruption of the Opal Stop Codon Attenuates Chikungunya Virus-Induced
RT Arthritis and Pathology.";
RL MBio 8:0-0(2017).
RN [15]
RP FUNCTION (PROTEASE NSP2), DOMAIN (PROTEASE NSP2), AND MUTAGENESIS OF
RP PRO-1253 AND 1184-LYS-ARG-1185.
RX PubMed=29925658; DOI=10.1128/jvi.01008-18;
RA Goeertz G.P., McNally K.L., Robertson S.J., Best S.M., Pijlman G.P.,
RA Fros J.J.;
RT "The methyltransferase-like domain of Chikungunya virus nsP2 inhibits the
RT interferon response by promoting the nuclear export of STAT1.";
RL J. Virol. 92:0-0(2018).
RN [16]
RP PALMITOYLATION AT CYS-417 (MRNA-CAPPING ENZYME NSP1), PALMITOYLATION AT
RP CYS-419 (MRNA-CAPPING ENZYME NSP1), SUBCELLULAR LOCATION (MRNA-CAPPING
RP ENZYME NSP1), MUTAGENESIS OF CYS-417 AND CYS-419, AND FUNCTION
RP (MRNA-CAPPING ENZYME NSP1).
RX PubMed=30404808; DOI=10.1128/jvi.01747-18;
RA Zhang N., Zhao H., Zhang L.;
RT "Fatty acid synthase promotes the palmitoylation of Chikungunya virus
RT nsP1.";
RL J. Virol. 0:0-0(2018).
RN [17]
RP INTERACTION WITH HOST G3BP1 (NON-STRUCTURAL PROTEIN 3), INTERACTION WITH
RP HOST G3BP2 (NON-STRUCTURAL PROTEIN 3), DOMAIN (NON-STRUCTURAL PROTEIN 3),
RP INTERACTION WITH HOST NAP1L1 (NON-STRUCTURAL PROTEIN 3), AND INTERACTION
RP WITH HOST NAP1L4 (NON-STRUCTURAL PROTEIN 3).
RX PubMed=29899097; DOI=10.1128/jvi.00838-18;
RA Meshram C.D., Agback P., Shiliaev N., Urakova N., Mobley J.A., Agback T.,
RA Frolova E.I., Frolov I.;
RT "Multiple Host Factors Interact with the Hypervariable Domain of
RT Chikungunya Virus nsP3 and Determine Viral Replication in Cell-Specific
RT Mode.";
RL J. Virol. 92:0-0(2018).
RN [18]
RP DOMAIN (NON-STRUCTURAL PROTEIN 3), AND MUTAGENESIS OF 1593-VAL-PRO-1594 AND
RP 1595-CYS--CYS-1597.
RC STRAIN=Isolate LR2006 OPY1;
RX PubMed=30668592; DOI=10.1371/journal.ppat.1007239;
RA Gao Y., Goonawardane N., Ward J., Tuplin A., Harris M.;
RT "Multiple roles of the non-structural protein 3 (nsP3) alphavirus unique
RT domain (AUD) during Chikungunya virus genome replication and
RT transcription.";
RL PLoS Pathog. 15:e1007239-e1007239(2019).
RN [19]
RP INTERACTION WITH HOST CD2AP (NON-STRUCTURAL PROTEIN 3), DOMAIN
RP (NON-STRUCTURAL PROTEIN 3), AND INTERACTION WITH HOST SH3KBP1
RP (NON-STRUCTURAL PROTEIN 3).
RX PubMed=31493651; DOI=10.1016/j.virol.2019.08.022;
RA Agback P., Dominguez F., Pustovalova Y., Lukash T., Shiliaev N.,
RA Orekhov V.Y., Frolov I., Agback T., Frolova E.I.;
RT "Structural characterization and biological function of bivalent binding of
RT CD2AP to intrinsically disordered domain of chikungunya virus nsP3
RT protein.";
RL Virology 537:130-142(2019).
RN [20]
RP INTERACTION WITH HOST DHX9 (NON-STRUCTURAL PROTEIN 3), AND DOMAIN
RP (NON-STRUCTURAL PROTEIN 3).
RX PubMed=30463980; DOI=10.1128/jvi.01764-18;
RA Matkovic R., Bernard E., Fontanel S., Eldin P., Chazal N., Hassan Hersi D.,
RA Merits A., Peloponese J.M. Jr., Briant L.;
RT "The Host DHX9 DExH-Box Helicase Is Recruited to Chikungunya Virus
RT Replication Complexes for Optimal Genomic RNA Translation.";
RL J. Virol. 93:0-0(2019).
RN [21]
RP INTERACTION WITH HOST FHL1 (NON-STRUCTURAL PROTEIN 3).
RC STRAIN=Isolate CHIKV21;
RX PubMed=31554973; DOI=10.1038/s41586-019-1578-4;
RA Meertens L., Hafirassou M.L., Couderc T., Bonnet-Madin L., Kril V.,
RA Kuemmerer B.M., Labeau A., Brugier A., Simon-Loriere E.,
RA Burlaud-Gaillard J., Doyen C., Pezzi L., Goupil T., Rafasse S.,
RA Vidalain P.O., Bertrand-Legout A., Gueneau L., Juntas-Morales R.,
RA Ben Yaou R., Bonne G., de Lamballerie X., Benkirane M., Roingeard P.,
RA Delaugerre C., Lecuit M., Amara A.;
RT "FHL1 is a major host factor for chikungunya virus infection.";
RL Nature 574:259-263(2019).
RN [22]
RP INTERACTION WITH HOST FHL1 (NON-STRUCTURAL PROTEIN 3).
RX PubMed=33055253; DOI=10.1128/jvi.01672-20;
RA Lukash T., Agback T., Dominguez F., Shiliaev N., Meshram C., Frolova E.I.,
RA Agback P., Frolov I.;
RT "Structural and Functional Characterization of Host FHL1 Protein
RT Interaction with Hypervariable Domain of Chikungunya Virus nsP3 Protein.";
RL J. Virol. 95:0-0(2020).
RN [23]
RP INTERACTION WITH HOST STING1 (NON-STRUCTURAL PROTEIN 1).
RX PubMed=33057424; DOI=10.1371/journal.ppat.1008999;
RA Webb L.G., Veloz J., Pintado-Silva J., Zhu T., Rangel M.V., Mutetwa T.,
RA Zhang L., Bernal-Rubio D., Figueroa D., Carrau L., Fenutria R., Potla U.,
RA Reid S.P., Yount J.S., Stapleford K.A., Aguirre S., Fernandez-Sesma A.;
RT "Chikungunya virus antagonizes cGAS-STING mediated type-I interferon
RT responses by degrading cGAS.";
RL PLoS Pathog. 16:e1008999-e1008999(2020).
RN [24] {ECO:0007744|PDB:3GPG, ECO:0007744|PDB:3GPO, ECO:0007744|PDB:3GPQ}
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 1334-1493 IN COMPLEX WITH
RP ADP-RIBOSE, MUTAGENESIS OF ASP-1343; ASN-1357 AND TYR-1447, AND CATALYTIC
RP ACTIVITY (NON-STRUCTURAL PROTEIN 3).
RX PubMed=19386706; DOI=10.1128/jvi.00189-09;
RA Malet H., Coutard B., Jamal S., Dutartre H., Papageorgiou N., Neuvonen M.,
RA Ahola T., Forrester N., Gould E.A., Lafitte D., Ferron F., Lescar J.,
RA Gorbalenya A.E., de Lamballerie X., Canard B.;
RT "The crystal structures of Chikungunya and Venezuelan equine encephalitis
RT virus nsP3 macro domains define a conserved adenosine binding pocket.";
RL J. Virol. 83:6534-6545(2009).
RN [25] {ECO:0007744|PDB:5I22}
RP STRUCTURE BY NMR OF 1728-1744.
RX PubMed=27268056; DOI=10.1074/jbc.m116.732412;
RA Tossavainen H., Aitio O., Hellman M., Saksela K., Permi P.;
RT "Structural Basis of the High Affinity Interaction between the Alphavirus
RT Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2.";
RL J. Biol. Chem. 291:16307-16317(2016).
RN [26] {ECO:0007744|PDB:6Z0U, ECO:0007744|PDB:6Z0V}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.60 ANGSTROMS) OF 1-472, AND SUBUNIT
RP (NON-STRUCTURAL PROTEIN 1).
RX PubMed=33328629; DOI=10.1038/s41586-020-3036-8;
RA Jones R., Bragagnolo G., Arranz R., Reguera J.;
RT "Capping pores of alphavirus nsP1 gate membranous viral replication
RT factories.";
RL Nature 589:615-619(2021).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS) OF 1-516 IN COMPLEX WITH ZINC,
RP SUBUNIT (NON-STRUCTURAL PROTEIN 1), ACTIVE SITE (NON-STRUCTURAL PROTEIN 1),
RP AND FUNCTION (NON-STRUCTURAL PROTEIN 1).
RX PubMed=33730549; DOI=10.1016/j.chom.2021.02.018;
RA Zhang K., Law Y.S., Law M.C.Y., Tan Y.B., Wirawan M., Luo D.;
RT "Structural insights into viral RNA capping and plasma membrane targeting
RT by Chikungunya virus nonstructural protein 1.";
RL Cell Host Microbe 0:0-0(2021).
CC -!- FUNCTION: [Polyprotein P1234]: Inactive precursor of the viral
CC replicase, which is activated by cleavages carried out by the viral
CC protease nsP2. {ECO:0000269|PubMed:27845418}.
CC -!- FUNCTION: [Polyprotein P123]: The early replication complex formed by
CC the polyprotein P123 and nsP4 synthesizes minus-strand RNAs (By
CC similarity). As soon P123 is cleaved into mature proteins, the plus-
CC strand RNAs synthesis begins (By similarity).
CC {ECO:0000250|UniProtKB:P03317}.
CC -!- FUNCTION: [mRNA-capping enzyme nsP1]: Cytoplasmic capping enzyme that
CC catalyzes two virus-specific reactions: methyltransferase and
CC guanylyltransferase (By similarity). mRNA-capping is necessary since
CC all viral RNAs are synthesized in the cytoplasm, and host capping
CC enzymes are restricted to the nucleus (Probable). The enzymatic
CC reaction involves a covalent link between 7-methyl-GMP and nsP1,
CC whereas eukaryotic capping enzymes form a covalent complex only with
CC GMP (By similarity). nsP1 capping consists in the following reactions:
CC GTP is first methylated into 7-methyl-GMP and then is covalently linked
CC to nsP1 to form the m7GMp-nsP1 complex from which 7-methyl-GMP complex
CC is transferred to the mRNA to create the cap structure (By similarity).
CC NsP1 is also needed for the initiation of the minus-strand RNAs
CC synthesis (By similarity). At the initiation of virus replication,
CC mediates the assembly of the viral replication complex made of the non-
CC structural proteins, the association of this complex with the inner
CC face of the plasma membrane and the formation of membranous spherules
CC that serve as replication complex factories (PubMed:33730549). Forms
CC the neck of these spherules with a central channel for mediating
CC communication and the passage of RNA, nucleotides, and small proteins
CC between the viral replication complex and the host cytoplasm
CC (PubMed:33730549). Palmitoylated nsP1 is remodeling host cell
CC cytoskeleton, and induces filopodium-like structure formation at the
CC surface of the host cell (PubMed:30404808).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000269|PubMed:30404808,
CC ECO:0000269|PubMed:33730549}.
CC -!- FUNCTION: [Protease nsP2]: Multifunctional protein whose N-terminus is
CC part of the RNA polymerase complex and displays NTPase, RNA
CC triphosphatase and helicase activities (PubMed:21811589,
CC PubMed:24407286). NTPase and RNA triphosphatase are involved in viral
CC RNA capping and helicase keeps a check on the dsRNA replication
CC intermediates (By similarity). The C-terminus harbors a protease that
CC specifically cleaves the polyproteins and releases the mature proteins
CC (PubMed:27845418, PubMed:26597768). Required for the shutoff of minus-
CC strand RNAs synthesis (By similarity). Specifically inhibits the host
CC IFN response by promoting the nuclear export of host STAT1
CC (PubMed:29925658). Also inhibits host transcription by inducing the
CC rapid proteasome-dependent degradation of POLR2A, a catalytic subunit
CC of the RNAPII complex (PubMed:22514352). The resulting inhibition of
CC cellular protein synthesis serves to ensure maximal viral gene
CC expression and to evade host immune response (Probable).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P08411,
CC ECO:0000269|PubMed:21811589, ECO:0000269|PubMed:22514352,
CC ECO:0000269|PubMed:24407286, ECO:0000269|PubMed:26597768,
CC ECO:0000269|PubMed:27845418, ECO:0000269|PubMed:29925658,
CC ECO:0000305|PubMed:22514352}.
CC -!- FUNCTION: [Non-structural protein 3]: Seems to be essential for minus-
CC strand RNAs and subgenomic 26S mRNAs synthesis (By similarity).
CC Displays mono-ADP-ribosylhydrolase activity (PubMed:28143925,
CC PubMed:28150709). ADP-ribosylation is a post-translational modification
CC that controls various processes of the host cell and the virus probably
CC needs to revert it for optimal viral replication (PubMed:28143925,
CC PubMed:28150709). Binds proteins of G3BP family and sequesters them
CC into the viral RNA replication complexes thereby inhibiting the
CC formation of host stress granules on viral mRNAs (PubMed:25653451). The
CC nsp3-G3BP complexes bind viral RNAs and probably orchestrate the
CC assembly of viral replication complexes, thanks to the ability of G3BP
CC family members to self-assemble and bind DNA (PubMed:27509095,
CC PubMed:27383630) (Probable). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000269|PubMed:25653451, ECO:0000269|PubMed:27383630,
CC ECO:0000269|PubMed:27509095, ECO:0000269|PubMed:28143925,
CC ECO:0000269|PubMed:28150709, ECO:0000305|PubMed:25653451}.
CC -!- FUNCTION: [RNA-directed RNA polymerase nsP4]: RNA dependent RNA
CC polymerase (By similarity). Replicates genomic and antigenomic RNA by
CC recognizing replications specific signals. The early replication
CC complex formed by the polyprotein P123 and nsP4 synthesizes minus-
CC strand RNAs (By similarity). The late replication complex composed of
CC fully processed nsP1-nsP4 is responsible for the production of genomic
CC and subgenomic plus-strand RNAs (By similarity).
CC {ECO:0000250|UniProtKB:P03317}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + S-adenosyl-L-methionine = N(7)-methyl-GTP + S-adenosyl-
CC L-homocysteine; Xref=Rhea:RHEA:46948, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:87133;
CC Evidence={ECO:0000250|UniProtKB:P27282};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[nsP1 protein]-L-histidine + N(7)-methyl-GTP = [nsP1 protein]-
CC N(tele)-(N(7)-methylguanosine 5'-phospho)-L-histidine + diphosphate;
CC Xref=Rhea:RHEA:54792, Rhea:RHEA-COMP:13994, Rhea:RHEA-COMP:13995,
CC ChEBI:CHEBI:29979, ChEBI:CHEBI:33019, ChEBI:CHEBI:87133,
CC ChEBI:CHEBI:138334; Evidence={ECO:0000250|UniProtKB:P27282};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54793;
CC Evidence={ECO:0000250|UniProtKB:P27282};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[nsP1 protein]-N(tele)-(N(7)-methylguanosine 5'-phospho)-L-
CC histidine + a 5'-end diphospho-(purine-ribonucleoside) in mRNA + H(+)
CC = [nsP1 protein]-L-histidine + a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-(purine-ribonucleoside) in mRNA;
CC Xref=Rhea:RHEA:54800, Rhea:RHEA-COMP:12925, Rhea:RHEA-COMP:13929,
CC Rhea:RHEA-COMP:13994, Rhea:RHEA-COMP:13995, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29979, ChEBI:CHEBI:133968, ChEBI:CHEBI:138276,
CC ChEBI:CHEBI:138334; Evidence={ECO:0000250|UniProtKB:P27282};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end triphospho-(purine-ribonucleoside) in mRNA + H2O = a
CC 5'-end diphospho-(purine-ribonucleoside) in mRNA + H(+) + phosphate;
CC Xref=Rhea:RHEA:11008, Rhea:RHEA-COMP:13929, Rhea:RHEA-COMP:13942,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:138276, ChEBI:CHEBI:138288; EC=3.1.3.33;
CC Evidence={ECO:0000269|PubMed:21811589};
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:0000269|PubMed:21811589, ECO:0000269|PubMed:24407286};
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:0000269|PubMed:21811589, ECO:0000269|PubMed:24407286};
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=4-O-(ADP-D-ribosyl)-L-aspartyl-[protein] + H2O = ADP-D-ribose
CC + H(+) + L-aspartyl-[protein]; Xref=Rhea:RHEA:54428, Rhea:RHEA-
CC COMP:9867, Rhea:RHEA-COMP:13832, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29961, ChEBI:CHEBI:57967,
CC ChEBI:CHEBI:138102; Evidence={ECO:0000269|PubMed:28143925,
CC ECO:0000269|PubMed:28150709};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54429;
CC Evidence={ECO:0000269|PubMed:28143925, ECO:0000269|PubMed:28150709};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-O-(ADP-D-ribosyl)-L-glutamyl-[protein] + H2O = ADP-D-ribose
CC + H(+) + L-glutamyl-[protein]; Xref=Rhea:RHEA:58248, Rhea:RHEA-
CC COMP:10208, Rhea:RHEA-COMP:15089, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29973, ChEBI:CHEBI:57967,
CC ChEBI:CHEBI:142540; Evidence={ECO:0000269|PubMed:28143925,
CC ECO:0000269|PubMed:28150709};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58249;
CC Evidence={ECO:0000269|PubMed:28143925, ECO:0000269|PubMed:28150709};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + RNA(n) = diphosphate + RNA(n)-3'-adenine ribonucleotide;
CC Xref=Rhea:RHEA:11332, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17347,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:140395,
CC ChEBI:CHEBI:173115; EC=2.7.7.19;
CC Evidence={ECO:0000250|UniProtKB:P03317};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP-beta-D-ribose 1''-phosphate + H2O = ADP-D-ribose +
CC phosphate; Xref=Rhea:RHEA:25029, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57967, ChEBI:CHEBI:58753; EC=3.1.3.84;
CC Evidence={ECO:0000269|PubMed:19386706};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25030;
CC Evidence={ECO:0000269|PubMed:19386706};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P03317};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P03317};
CC Note=For nsP4 adenylyltransferase activity; Mn(2+) supports catalysis
CC at 60% of the levels observed with Mg(2+).
CC {ECO:0000250|UniProtKB:P03317};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Note=For nsP4 RNA-directed RNA polymerase activity.
CC {ECO:0000250|UniProtKB:P03317};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P27282};
CC Note=For nsP1 guanylylation. {ECO:0000250|UniProtKB:P27282};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Note=For nsP2 RNA triphosphatase activity.
CC {ECO:0000269|PubMed:21811589, ECO:0000269|PubMed:24407286};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Note=For nsP2 NTPase activity. {ECO:0000269|PubMed:21811589,
CC ECO:0000269|PubMed:24407286};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.2 for nsP2 NTPase. {ECO:0000269|PubMed:21811589,
CC ECO:0000269|PubMed:24407286};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius for nsP2 NTPase.
CC {ECO:0000269|PubMed:21811589};
CC -!- SUBUNIT: [mRNA-capping enzyme nsP1]: Homododecamer (PubMed:33328629,
CC PubMed:33730549). The enzyme forms a membrane-associated dodecameric
CC ring with a central channel for the exchange of between the viral
CC replication factories and the host cytoplasm (PubMed:33328629,
CC PubMed:33730549). Interacts with non-structural protein 3
CC (PubMed:22951312). Interacts with RNA-directed RNA polymerase nsP4
CC (PubMed:22951312). Interacts with protease nsP2 (PubMed:22951312).
CC Interacts with itself (PubMed:22951312). Interacts with host STING1;
CC this interaction results in inhibition of cGAS-STING signaling and
CC increased levels of palmitoylation and protein stabilization of nsP1
CC (PubMed:33057424). {ECO:0000269|PubMed:22951312,
CC ECO:0000269|PubMed:33057424, ECO:0000269|PubMed:33328629,
CC ECO:0000269|PubMed:33730549}.
CC -!- SUBUNIT: [Non-structural protein 3]: Interacts with mRNA-capping enzyme
CC nsP1 (PubMed:22951312). Interacts (via C-terminus) with host G3BP1;
CC this interaction inhibits the formation of host stress granules on
CC viral mRNAs and the nsp3-G3BP1 complexes bind viral RNAs and probably
CC orchestrate the assembly of viral replication complexes
CC (PubMed:24623412, PubMed:27383630, PubMed:27509095, PubMed:29899097).
CC Interacts (via C-terminus) with host G3BP2; this interaction inhibits
CC the formation of host stress granules on viral mRNAs and the nsp3-G3BP2
CC complexes bind viral RNAs and probably orchestrate the assembly of
CC viral replication complexes (Probable). Interacts (via C-terminus) with
CC host NAP1L1 (PubMed:29899097). Interacts (via C-terminus) with host
CC NAP1L4 (PubMed:29899097). Interacts (via C-terminus) with host DHX9;
CC this interaction allows the recruitment of DHX9 to the plasma membrane,
CC where it associates with viral replication complexes and may play a
CC role in the translation-to-replication switch (PubMed:30463980).
CC Interacts (via C-terminus) with host FHL1 (via LIM domain 1); this
CC interaction is required for viral RNA replication (PubMed:31554973,
CC PubMed:33055253). Interacts (via C-terminus) with host CD2AP; this
CC interaction plays a role in initiation of viral replication
CC (PubMed:31493651). Interacts (via C-terminus) with host SH3KBP1; this
CC interaction plays a role in initiation of viral replication
CC (PubMed:31493651). {ECO:0000269|PubMed:22951312,
CC ECO:0000269|PubMed:24623412, ECO:0000269|PubMed:27383630,
CC ECO:0000269|PubMed:27509095, ECO:0000269|PubMed:29899097,
CC ECO:0000269|PubMed:30463980, ECO:0000269|PubMed:31493651,
CC ECO:0000269|PubMed:31554973, ECO:0000269|PubMed:33055253,
CC ECO:0000305|PubMed:29899097}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase nsP4]: Interacts with mRNA-
CC capping enzyme nsP1 (PubMed:22951312). Interacts with protease nsP2
CC (PubMed:22951312). interacts with itself (PubMed:22951312).
CC {ECO:0000269|PubMed:22951312}.
CC -!- SUBUNIT: [Protease nsP2]: Interacts with RNA-directed RNA polymerase
CC nsP4 (PubMed:22951312). Interacts with mRNA-capping enzyme nsP1
CC (PubMed:22951312). Interacts with KPNA1/karyopherin-alpha1; this
CC interaction probably allows the active transport of protease nsP2 into
CC the host nucleus (By similarity). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000250|UniProtKB:P27282, ECO:0000269|PubMed:22951312}.
CC -!- SUBCELLULAR LOCATION: [Polyprotein P1234]: Host cytoplasmic vesicle
CC membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}.
CC Note=Part of cytoplasmic vesicles, which are probably formed at the
CC plasma membrane and internalized leading to late endosomal/lysosomal
CC spherules containing the replication complex. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Polyprotein P123]: Host cytoplasmic vesicle
CC membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}.
CC Note=Part of cytoplasmic vesicles, which are probably formed at the
CC plasma membrane and internalized leading to late endosomal/lysosomal
CC spherules containing the replication complex. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [mRNA-capping enzyme nsP1]: Host cytoplasmic
CC vesicle membrane {ECO:0000250|UniProtKB:P08411}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P08411}. Host cell membrane
CC {ECO:0000250|UniProtKB:P08411}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P08411}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P08411}. Host cell projection, host filopodium
CC {ECO:0000269|PubMed:30404808}. Note=In the late phase of infection, the
CC polyprotein is quickly cleaved before localization to cellular
CC membranes. Then a fraction of nsP1 localizes to the inner surface of
CC the plasma membrane and its filopodial extensions. Only the
CC palmitoylated nsP1 localizes to the host filopodia (PubMed:30404808).
CC NsP1 is also part of cytoplasmic vesicles, which are probably formed at
CC the plasma membrane and internalized leading to late
CC endosomal/lysosomal spherules containing the replication complex (By
CC similarity). {ECO:0000250|UniProtKB:P08411,
CC ECO:0000269|PubMed:30404808}.
CC -!- SUBCELLULAR LOCATION: [Protease nsP2]: Host cytoplasmic vesicle
CC membrane {ECO:0000250|UniProtKB:P08411}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P08411}. Host nucleus
CC {ECO:0000250|UniProtKB:P27282}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P27282}. Note=In the late phase of infection,
CC the polyprotein is quickly cleaved before localization to cellular
CC membranes. Then approximately half of nsP2 is found in the nucleus (By
CC similarity). Shuttles between cytoplasm and nucleus (By similarity).
CC NsP2 is also part of cytoplasmic vesicles, which are probably formed at
CC the plasma membrane and internalized leading to late
CC endosomal/lysosomal spherules containing the replication complex (By
CC similarity). {ECO:0000250|UniProtKB:P08411,
CC ECO:0000250|UniProtKB:P27282}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 3]: Host cytoplasmic
CC vesicle membrane {ECO:0000250|UniProtKB:P03317}; Peripheral membrane
CC protein {ECO:0000305}. Note=In the late phase of infection, the
CC polyprotein is quickly cleaved before localization to cellular
CC membranes. Then nsP3 forms aggregates in cytoplasm (By similarity).
CC NsP3 is also part of cytoplasmic vesicles, which are probably formed at
CC the plasma membrane and internalized leading to late
CC endosomal/lysosomal spherules containing the replication complex (By
CC similarity). {ECO:0000250|UniProtKB:P03317}.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase nsP4]: Host
CC cytoplasmic vesicle membrane; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P08411}. Note=NsP4 is part of cytoplasmic
CC vesicles, which are probably formed at the plasma membrane and
CC internalized leading to late endosomal/lysosomal spherules containing
CC the replication complex. {ECO:0000250|UniProtKB:P08411}.
CC -!- DOMAIN: [mRNA-capping enzyme nsP1]: The N-terminus binds a zinc ion
CC which stabilizes this region (PubMed:33730549). The C-terminus is
CC disordered (PubMed:33730549). {ECO:0000269|PubMed:33730549}.
CC -!- DOMAIN: [Protease nsP2]: The N-terminus exhibits NTPase and RNA
CC triphosphatase activities and is proposed to have helicase activity,
CC whereas the C-terminus possesses protease activity (PubMed:24407286).
CC Contains a nuclear localization signal and a nuclear export signal,
CC these two motifs are probably involved in the shuttling between the
CC cytoplasm and the nucleus of nsP2 (By similarity). The C-terminus is
CC required for promoting the export of host STAT1 (PubMed:29925658).
CC {ECO:0000250|UniProtKB:P27282, ECO:0000269|PubMed:24407286,
CC ECO:0000269|PubMed:29925658}.
CC -!- DOMAIN: [Non-structural protein 3]: In the N-terminus, the macro domain
CC displays a mono-ADP-ribosylhydrolase activity (PubMed:28143925,
CC PubMed:28150709). The central part called, the alphavirus unique domain
CC (AUD) has a zinc-binding function (PubMed:30668592). The C-terminus
CC region, also called hypervariable domain (HVD), is mainly disordered
CC and binds several host proteins (PubMed:29899097, PubMed:31493651,
CC PubMed:30463980). This intrinsically disordered domain contains 2 SH3
CC domain-binding sites and 2 FGDF motifs necessary and sufficient for the
CC formation of nsP3/G3BP complexes (PubMed:27383630, PubMed:27509095,
CC PubMed:29899097). {ECO:0000269|PubMed:27383630,
CC ECO:0000269|PubMed:27509095, ECO:0000269|PubMed:28143925,
CC ECO:0000269|PubMed:28150709, ECO:0000269|PubMed:29899097,
CC ECO:0000269|PubMed:30463980, ECO:0000269|PubMed:30668592,
CC ECO:0000269|PubMed:31493651}.
CC -!- PTM: [Polyprotein P1234]: Specific enzymatic cleavages in vivo yield
CC mature proteins (PubMed:27845418). The processing of the polyprotein is
CC temporally regulated (By similarity). In early stages (1.7 hpi), P1234
CC is first cleaved in trans through its nsP2 protease activity, releasing
CC P123 and nsP4, which associate to form the early replication complex
CC (By similarity). At the same time, P1234 is also cut at the nsP1/nsP2
CC site early in infection but with lower efficiency (By similarity).
CC After replication of the viral minus-strand RNAs (4 hpi), the
CC polyproteins are cut at the nsP1/nsP2 and nsP2/nsP3 sites very
CC efficiently, preventing accumulation of P123 and P1234 and allowing the
CC formation of the late replication complex (By similarity). NsP3/nsP4
CC site is not cleaved anymore and P34 is produced rather than nsP4 (By
CC similarity). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000269|PubMed:27845418}.
CC -!- PTM: [Polyprotein P123]: Specific enzymatic cleavages in vivo yield
CC mature proteins (By similarity). The processing of the polyprotein is
CC temporally regulated (By similarity). In early stages (1.7 hpi), P123
CC is cleaved at the nsP1/nsP2 site with low efficiency (By similarity).
CC After replication of the viral minus-strand RNAs (4 hpi), the
CC polyproteins are cut at the nsP1/nsP2 and nsP2/nsP3 sites very
CC efficiently, preventing accumulation of P123 and allowing the formation
CC of the late replication complex (By similarity).
CC {ECO:0000250|UniProtKB:P03317}.
CC -!- PTM: [mRNA-capping enzyme nsP1]: Palmitoylated by host
CC palmitoyltransferases ZDHHC2 and ZDHHC19 (PubMed:30404808).
CC Palmitoylation is increased by the interacton with host STING1
CC (PubMed:33057424). {ECO:0000269|PubMed:30404808,
CC ECO:0000269|PubMed:33057424}.
CC -!- PTM: [Non-structural protein 3]: Phosphorylated by host on serines and
CC threonines. {ECO:0000250|UniProtKB:P08411}.
CC -!- PTM: [RNA-directed RNA polymerase nsP4]: Ubiquitinated; targets the
CC protein for rapid degradation via the ubiquitin system (By similarity).
CC Nsp4 is present in extremely low quantities due to low frequency of
CC translation through the amber stop-codon and the degradation by the
CC ubiquitin pathway (By similarity). {ECO:0000250|UniProtKB:P03317}.
CC -!- MISCELLANEOUS: Viral replication produces dsRNA in the late phase of
CC infection, resulting in a strong activation of host EIF2AK2/PKR,
CC leading to almost complete phosphorylation of EIF2A (By similarity).
CC This inactivates completely cellular translation initiation, resulting
CC shutoff of host proteins synthesis (By similarity). However,
CC phosphorylation of EIF2A is probably not the only mechanism responsible
CC for the host translation shutoff (By similarity). The viral translation
CC can still occur normally because it relies on a hairpin structure in
CC the coding region of sgRNA and is EIF2A-, EIF2D-, EIF4G- EIF4A-
CC independent (By similarity). {ECO:0000250|UniProtKB:P03317}.
CC -!- CAUTION: There is no stop codon readthrough before nsP4 like in other
CC CHIKV strains. The opal termination codon may have been mutated to a
CC sense codon on passage in cell culture. The presence of an opal codon
CC may be a requirement for viral maintenance in both vertebrate and
CC invertebrate hosts and a selective advantage may be conferred in cell
CC culture for the sense codon (PubMed:29138302).
CC {ECO:0000269|PubMed:29138302, ECO:0000305}.
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DR EMBL; AF369024; AAN05101.1; -; Genomic_RNA.
DR RefSeq; NP_690588.1; NC_004162.2.
DR PDB; 3GPG; X-ray; 1.65 A; A/B/C/D=1334-1493.
DR PDB; 3GPO; X-ray; 1.90 A; A/B/C/D=1334-1493.
DR PDB; 3GPQ; X-ray; 2.00 A; A/B/C/D=1334-1493.
DR PDB; 3TRK; X-ray; 2.40 A; A=1006-1326.
DR PDB; 4TU0; X-ray; 2.30 A; A/B/C/D=1334-1493.
DR PDB; 5I22; NMR; -; B=1728-1744.
DR PDB; 6VUQ; X-ray; 1.64 A; A/B/C/D=1334-1493.
DR PDB; 6W7H; X-ray; 1.95 A; A/B/C/D=1334-1493.
DR PDB; 6W8K; X-ray; 1.80 A; A/B/C/D=1334-1493.
DR PDB; 6W8M; X-ray; 1.75 A; A/B/C/D=1334-1493.
DR PDB; 6W8Q; X-ray; 2.34 A; A/B/C/D=1334-1493.
DR PDB; 6W8Y; X-ray; 2.10 A; A/B/C/D=1334-1493.
DR PDB; 6W8Z; X-ray; 1.90 A; A/B/C/D=1334-1493.
DR PDB; 6W91; X-ray; 2.21 A; A/B/C/D=1334-1493.
DR PDB; 6Z0U; EM; 2.90 A; A/BA/C/DA/E/FA/G/HA/I/JA/K/LA/M/NA/O/PA/Q/RA/S/TA/V/VA/X/Z=1-472.
DR PDB; 6Z0V; EM; 2.60 A; A/C/E/G/I/K/M/O/Q/S/V/X=1-472.
DR PDB; 7DOP; EM; 2.38 A; A/B/C/D/E/F/G/H/I/J/K/L=1-516.
DR PDBsum; 3GPG; -.
DR PDBsum; 3GPO; -.
DR PDBsum; 3GPQ; -.
DR PDBsum; 3TRK; -.
DR PDBsum; 4TU0; -.
DR PDBsum; 5I22; -.
DR PDBsum; 6VUQ; -.
DR PDBsum; 6W7H; -.
DR PDBsum; 6W8K; -.
DR PDBsum; 6W8M; -.
DR PDBsum; 6W8Q; -.
DR PDBsum; 6W8Y; -.
DR PDBsum; 6W8Z; -.
DR PDBsum; 6W91; -.
DR PDBsum; 6Z0U; -.
DR PDBsum; 6Z0V; -.
DR PDBsum; 7DOP; -.
DR BMRB; Q8JUX6; -.
DR SMR; Q8JUX6; -.
DR BindingDB; Q8JUX6; -.
DR ChEMBL; CHEMBL4295622; -.
DR MEROPS; C09.001; -.
DR PRIDE; Q8JUX6; -.
DR GeneID; 956309; -.
DR KEGG; vg:956309; -.
DR BRENDA; 3.2.2.B6; 11217.
DR BRENDA; 3.4.22.B79; 11217.
DR EvolutionaryTrace; Q8JUX6; -.
DR Proteomes; UP000000569; Genome.
DR GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044176; C:host cell filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0032574; F:5'-3' RNA helicase activity; IDA:GO_Central.
DR GO; GO:0047407; F:ADP-ribosyl-[dinitrogen reductase] hydrolase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IMP: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:0008174; F:mRNA methyltransferase activity; IEA:InterPro.
DR GO; GO:0017111; F:nucleoside-triphosphatase activity; IDA:UniProtKB.
DR GO; GO:0004651; F:polynucleotide 5'-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004652; F:polynucleotide adenylyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
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:0006370; P:7-methylguanosine mRNA capping; IEA:UniProtKB-KW.
DR GO; GO:0039690; P:positive stranded viral RNA replication; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0035617; P:stress granule disassembly; IDA:UniProtKB.
DR GO; GO:0039562; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT activity; IDA:UniProtKB.
DR GO; GO:0039563; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IEA:UniProtKB-KW.
DR GO; GO:0039523; P:suppression by virus of host mRNA transcription via inhibition of RNA polymerase II activity; IDA:UniProtKB.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR CDD; cd21557; Macro_X_Nsp3-like; 1.
DR Gene3D; 3.40.220.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR Gene3D; 3.90.70.110; -; 1.
DR InterPro; IPR027351; (+)RNA_virus_helicase_core_dom.
DR InterPro; IPR002588; Alphavirus-like_MT_dom.
DR InterPro; IPR002620; Alphavirus_nsp2pro.
DR InterPro; IPR044936; Alphavirus_nsp2pro_sf.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR002589; Macro_dom.
DR InterPro; IPR043472; Macro_dom-like.
DR InterPro; IPR044371; Macro_X_NSP3-like.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR001788; Tymovirus_RNA-dep_RNA_pol.
DR Pfam; PF01661; Macro; 1.
DR Pfam; PF01707; Peptidase_C9; 1.
DR Pfam; PF00978; RdRP_2; 1.
DR Pfam; PF01443; Viral_helicase1; 1.
DR Pfam; PF01660; Vmethyltransf; 1.
DR SMART; SM00506; A1pp; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF52949; SSF52949; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS51743; ALPHAVIRUS_MT; 1.
DR PROSITE; PS51154; MACRO; 1.
DR PROSITE; PS51520; NSP2PRO; 1.
DR PROSITE; PS51657; PSRV_HELICASE; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding;
KW Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host transcription shutoff by virus; GTP-binding; Helicase;
KW Host cell membrane; Host cell projection; Host cytoplasm;
KW Host cytoplasmic vesicle; Host gene expression shutoff by virus;
KW Host membrane; 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 RNA polymerase II by virus;
KW Inhibition of host STAT1 by virus; Lipoprotein; Membrane; Metal-binding;
KW Methyltransferase; mRNA capping; mRNA processing; Multifunctional enzyme;
KW Nucleotide-binding; Nucleotidyltransferase; Palmitate; Phosphoprotein;
KW Protease; Reference proteome; RNA suppression of termination; RNA-binding;
KW RNA-directed RNA polymerase; S-adenosyl-L-methionine; Thiol protease;
KW Transferase; Ubl conjugation; Viral immunoevasion; Viral RNA replication;
KW Zinc.
FT CHAIN 1..2474
FT /note="Polyprotein P1234"
FT /id="PRO_0000308395"
FT CHAIN 1..1863
FT /note="Polyprotein P123"
FT /id="PRO_0000227760"
FT CHAIN 1..535
FT /note="mRNA-capping enzyme nsP1"
FT /id="PRO_0000227761"
FT CHAIN 536..1333
FT /note="Protease nsP2"
FT /id="PRO_0000227762"
FT CHAIN 1334..1863
FT /note="Non-structural protein 3"
FT /id="PRO_0000227763"
FT CHAIN 1864..2474
FT /note="RNA-directed RNA polymerase nsP4"
FT /id="PRO_0000227764"
FT DOMAIN 28..259
FT /note="Alphavirus-like MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01079"
FT DOMAIN 690..842
FT /note="(+)RNA virus helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT DOMAIN 843..991
FT /note="(+)RNA virus helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT DOMAIN 1004..1327
FT /note="Peptidase C9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT DOMAIN 1334..1493
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 2228..2343
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 295..450
FT /note="Membrane-binding and oligomerization"
FT /evidence="ECO:0000269|PubMed:33328629"
FT REGION 482..502
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1005..1024
FT /note="Nucleolus localization signal"
FT /evidence="ECO:0000250|UniProtKB:P08411"
FT REGION 1651..1672
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1659..1857
FT /note="HVD"
FT /evidence="ECO:0000269|PubMed:31493651"
FT REGION 1726..1739
FT /note="Interaction with host CD2AP"
FT /evidence="ECO:0000269|PubMed:31493651"
FT REGION 1745..1793
FT /note="Interaction with host FHL1"
FT /evidence="ECO:0000269|PubMed:33055253"
FT REGION 1756..1767
FT /note="Interaction with host CD2AP"
FT /evidence="ECO:0000269|PubMed:31493651"
FT REGION 1820..1828
FT /note="Interaction with host CD2AP"
FT /evidence="ECO:0000269|PubMed:31493651"
FT MOTIF 1058..1067
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:P27282"
FT MOTIF 1182..1186
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P08411"
FT MOTIF 1812..1815
FT /note="FGDF; binding to host G3BP1"
FT /evidence="ECO:0000305|PubMed:24623412"
FT MOTIF 1830..1833
FT /note="FGDF; binding to host G3BP1"
FT /evidence="ECO:0000305|PubMed:24623412"
FT COMPBIAS 488..502
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1654..1672
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 37
FT /note="For mRNA-capping enzyme nsP1 activity"
FT /evidence="ECO:0000269|PubMed:33730549"
FT ACT_SITE 1013
FT /note="For cysteine protease nsP2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT ACT_SITE 1083
FT /note="For cysteine protease nsP2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT BINDING 79
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:33730549"
FT BINDING 129
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:33730549"
FT BINDING 134
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:33730549"
FT BINDING 141
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:33730549"
FT BINDING 721..728
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT BINDING 1343
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000269|PubMed:19386706"
FT BINDING 1357
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000269|PubMed:19386706"
FT BINDING 1365
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000269|PubMed:19386706"
FT BINDING 1445
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000269|PubMed:19386706"
FT BINDING 1446
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000269|PubMed:19386706"
FT BINDING 1447
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000269|PubMed:19386706"
FT BINDING 1595
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1597
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1620
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1638
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 37
FT /note="Involved in the phosphoramide link with 7-methyl-
FT GMP"
FT /evidence="ECO:0000250|UniProtKB:P27282"
FT SITE 535..536
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 1333..1334
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 1863..1864
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000269|PubMed:27845418"
FT LIPID 417
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000305|PubMed:30404808"
FT LIPID 419
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000305|PubMed:30404808"
FT MUTAGEN 417
FT /note="C->A: Loss of palmitoylation."
FT /evidence="ECO:0000269|PubMed:30404808"
FT MUTAGEN 419
FT /note="C->A: Loss of palmitoylation."
FT /evidence="ECO:0000269|PubMed:30404808"
FT MUTAGEN 727
FT /note="K->A: 5 fold reduction of NTPase activity and 50%
FT loss of RTPase activity."
FT /evidence="ECO:0000269|PubMed:21811589"
FT MUTAGEN 787..788
FT /note="DE->AA: 5 fold reduction of NTPase activity and 50%
FT loss of RTPase activity."
FT /evidence="ECO:0000269|PubMed:21811589"
FT MUTAGEN 1013
FT /note="C->A: Complete loss of nsP2 protease activity; when
FT associated with A-1017."
FT /evidence="ECO:0000269|PubMed:26597768,
FT ECO:0000269|PubMed:27845418"
FT MUTAGEN 1014
FT /note="W->A: Complete loss of nsP2 protease activity."
FT /evidence="ECO:0000269|PubMed:27845418"
FT MUTAGEN 1017
FT /note="S->A: Complete loss of nsP2 protease activity; when
FT associated with A-1013."
FT /evidence="ECO:0000269|PubMed:26597768,
FT ECO:0000269|PubMed:27845418"
FT MUTAGEN 1084
FT /note="W->A: Increased nsP2 protease activity."
FT /evidence="ECO:0000269|PubMed:26597768"
FT MUTAGEN 1084
FT /note="W->F: Decreased nsP2 protease activity."
FT /evidence="ECO:0000269|PubMed:26597768"
FT MUTAGEN 1184..1185
FT /note="KR->AA: Complete loss of nuclear localization and
FT inhibition of JAK/STAT signaling."
FT /evidence="ECO:0000269|PubMed:29925658"
FT MUTAGEN 1253
FT /note="P->A: Complete loss of host transcription shutoff,
FT still able to localize in the nucleus and inhibit JAK/STAT
FT signaling."
FT /evidence="ECO:0000269|PubMed:29925658"
FT MUTAGEN 1343
FT /note="D->A: Partial loss of ADP-ribose 1'' phosphate
FT phosphatase activity."
FT /evidence="ECO:0000269|PubMed:19386706"
FT MUTAGEN 1357
FT /note="N->A: Partial loss of mono-ADP-ribosylhydrolase
FT activity; complete loss of ADP-ribose 1'' phosphate
FT phosphatase activity."
FT /evidence="ECO:0000269|PubMed:19386706,
FT ECO:0000269|PubMed:28150709"
FT MUTAGEN 1357
FT /note="N->R,Y: Almost complete loss of mono-ADP-
FT ribosylhydrolase activity."
FT /evidence="ECO:0000269|PubMed:28150709"
FT MUTAGEN 1366
FT /note="V->A: Partial loss of mono-ADP-ribosylhydrolase
FT activity."
FT /evidence="ECO:0000269|PubMed:28150709"
FT MUTAGEN 1366
FT /note="V->E,F: Almost complete loss of mono-ADP-
FT ribosylhydrolase activity."
FT /evidence="ECO:0000269|PubMed:28150709"
FT MUTAGEN 1447
FT /note="Y->A: Partial loss of mono-ADP-ribosylhydrolase
FT activity; complete loss of ADP-ribose 1'' phosphate
FT phosphatase activity."
FT /evidence="ECO:0000269|PubMed:19386706,
FT ECO:0000269|PubMed:28150709"
FT MUTAGEN 1447
FT /note="Y->V,W: Almost complete loss of mono-ADP-
FT ribosylhydrolase activity."
FT /evidence="ECO:0000269|PubMed:28150709"
FT MUTAGEN 1593..1594
FT /note="VP->AA: Complete loss of replication."
FT /evidence="ECO:0000269|PubMed:30668592"
FT MUTAGEN 1595..1597
FT /note="CLC->ALA: Complete loss of replication."
FT /evidence="ECO:0000269|PubMed:30668592"
FT MUTAGEN 1812
FT /note="F->A: Complete loss of binding to host G3BP1; when
FT associated with A-1830."
FT /evidence="ECO:0000269|PubMed:27383630"
FT MUTAGEN 1830
FT /note="F->A: Complete loss of binding to host G3BP1; when
FT associated with A-1812."
FT /evidence="ECO:0000269|PubMed:27383630"
FT STRAND 4..8
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 10..12
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 14..21
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 27..29
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 38..53
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 60..64
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 68..71
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 75..80
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 89..102
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 113..124
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 146..152
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 158..166
FT /evidence="ECO:0007829|PDB:7DOP"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 172..178
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 181..184
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 197..201
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 208..212
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 224..228
FT /evidence="ECO:0007829|PDB:6Z0V"
FT STRAND 237..243
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 246..251
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 252..256
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 262..266
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 272..282
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 285..295
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 303..307
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 309..321
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 324..334
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 336..341
FT /evidence="ECO:0007829|PDB:7DOP"
FT TURN 342..344
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 345..347
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 352..363
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 384..403
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 417..419
FT /evidence="ECO:0007829|PDB:6Z0V"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 430..433
FT /evidence="ECO:0007829|PDB:7DOP"
FT STRAND 438..442
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 462..472
FT /evidence="ECO:0007829|PDB:7DOP"
FT HELIX 1013..1024
FT /evidence="ECO:0007829|PDB:3TRK"
FT HELIX 1031..1037
FT /evidence="ECO:0007829|PDB:3TRK"
FT HELIX 1039..1042
FT /evidence="ECO:0007829|PDB:3TRK"
FT HELIX 1049..1061
FT /evidence="ECO:0007829|PDB:3TRK"
FT HELIX 1065..1067
FT /evidence="ECO:0007829|PDB:3TRK"
FT STRAND 1075..1079
FT /evidence="ECO:0007829|PDB:3TRK"
FT STRAND 1088..1094
FT /evidence="ECO:0007829|PDB:3TRK"
FT HELIX 1097..1106
FT /evidence="ECO:0007829|PDB:3TRK"
FT HELIX 1108..1110
FT /evidence="ECO:0007829|PDB:3TRK"
FT STRAND 1119..1121
FT /evidence="ECO:0007829|PDB:3TRK"
FT TURN 1122..1125
FT /evidence="ECO:0007829|PDB:3TRK"
FT STRAND 1126..1129
FT /evidence="ECO:0007829|PDB:3TRK"
FT HELIX 1160..1163
FT /evidence="ECO:0007829|PDB:3TRK"
FT STRAND 1169..1177
FT /evidence="ECO:0007829|PDB:3TRK"
FT STRAND 1184..1191
FT /evidence="ECO:0007829|PDB:3TRK"
FT STRAND 1198..1201
FT /evidence="ECO:0007829|PDB:3TRK"
FT HELIX 1203..1205
FT /evidence="ECO:0007829|PDB:3TRK"
FT HELIX 1209..1211
FT /evidence="ECO:0007829|PDB:3TRK"
FT STRAND 1214..1220
FT /evidence="ECO:0007829|PDB:3TRK"
FT HELIX 1229..1246
FT /evidence="ECO:0007829|PDB:3TRK"
FT HELIX 1247..1250
FT /evidence="ECO:0007829|PDB:3TRK"
FT STRAND 1251..1261
FT /evidence="ECO:0007829|PDB:3TRK"
FT HELIX 1267..1277
FT /evidence="ECO:0007829|PDB:3TRK"
FT STRAND 1280..1286
FT /evidence="ECO:0007829|PDB:3TRK"
FT STRAND 1297..1304
FT /evidence="ECO:0007829|PDB:3TRK"
FT HELIX 1314..1323
FT /evidence="ECO:0007829|PDB:3TRK"
FT STRAND 1337..1342
FT /evidence="ECO:0007829|PDB:6VUQ"
FT HELIX 1344..1346
FT /evidence="ECO:0007829|PDB:6VUQ"
FT STRAND 1352..1355
FT /evidence="ECO:0007829|PDB:6VUQ"
FT HELIX 1365..1373
FT /evidence="ECO:0007829|PDB:6VUQ"
FT HELIX 1375..1378
FT /evidence="ECO:0007829|PDB:6VUQ"
FT STRAND 1388..1393
FT /evidence="ECO:0007829|PDB:6VUQ"
FT STRAND 1396..1401
FT /evidence="ECO:0007829|PDB:6VUQ"
FT TURN 1406..1408
FT /evidence="ECO:0007829|PDB:6VUQ"
FT HELIX 1411..1432
FT /evidence="ECO:0007829|PDB:6VUQ"
FT STRAND 1435..1439
FT /evidence="ECO:0007829|PDB:6VUQ"
FT HELIX 1445..1447
FT /evidence="ECO:0007829|PDB:3GPQ"
FT HELIX 1454..1465
FT /evidence="ECO:0007829|PDB:6VUQ"
FT STRAND 1470..1477
FT /evidence="ECO:0007829|PDB:6VUQ"
FT HELIX 1479..1490
FT /evidence="ECO:0007829|PDB:6VUQ"
SQ SEQUENCE 2474 AA; 275652 MW; 97D250B9EB5A3BB0 CRC64;
MDPVYVDIDA DSAFLKALQR AYPMFEVEPR QVTPNDHANA RAFSHLAIKL IEQEIDPDST
ILDIGSAPAR RMMSDRKYHC VCPMRSAEDP ERLANYARKL ASAAGKVLDR NISGKIGDLQ
AVMAVPDTET PTFCLHTDVS CRQRADVAIY QDVYAVHAPT SLYHQAIKGV RLAYWVGFDT
TPFMYNAMAG AYPSYSTNWA DEQVLKAKNI GLCSTDLTEG RRGKLSIMRG KKLEPCDRVL
FSVGSTLYPE SRKLLKSWHL PSVFHLKGKL SFTCRCDTVV SCEGYVVKRI TMSPGLYGKT
TGYAVTHHAD GFLMCKTTDT VDGERVSFSV CTYVPATICD QMTGILATEV TPEDAQKLLV
GLNQRIVVNG RTQRNTNTMK NYMIPVVAQA FSKWAKECRK DMEDEKLLGV RERTLTCCCL
WAFKKQKTHT VYKRPDTQSI QKVQAEFDSF VVPSLWSSGL SIPLRTRIKW LLSKVPKTDL
TPYSGDAQEA RDAEKEAEEE REAELTLEAL PPLQAAQEDV QVEIDVEQLE DRAGAGIIET
PRGAIKVTAQ PTDHVVGEYL VLSPQTVLRS QKLSLIHALA EQVKTCTHSG RAGRYAVEAY
DGRVLVPSGY AISPEDFQSL SESATMVYNE REFVNRKLHH IAMHGPALNT DEESYELVRA
ERTEHEYVYD VDQRRCCKKE EAAGLVLVGD LTNPPYHEFA YEGLKIRPAC PYKIAVIGVF
GVPGSGKSAI IKNLVTRQDL VTSGKKENCQ EITTDVMRQR GLEISARTVD SLLLNGCNRP
VDVLYVDEAF ACHSGTLLAL IALVRPRQKV VLCGDPKQCG FFNMMQMKVN YNHNICTQVY
HKSISRRCTL PVTAIVSSLH YEGKMRTTNE YNKPIVVDTT GSTKPDPGDL VLTCFRGWVK
QLQIDYRGHE VMTAAASQGL TRKGVYAVRQ KVNENPLYAS TSEHVNVLLT RTEGKLVWKT
LSGDPWIKTL QNPPKGNFKA TIKEWEVEHA SIMAGICSHQ MTFDTFQNKA NVCWAKSLVP
ILETAGIKLN DRQWSQIIQA FKEDKAYSPE VALNEICTRM YGVDLDSGLF SKPLVSVYYA
DNHWDNRPGG KMFGFNPEAA SILERKYPFT KGKWNINKQI CVTTRRIEDF NPTTNIIPAN
RRLPHSLVAE HRPVKGERME WLVNKINGHH VLLVSGCSLA LPTKRVTWVA PLGVRGADYT
YNLELGLPAT LGRYDLVVIN IHTPFRIHHY QQCVDHAMKL QMLGGDSLRL LKPGGSLLIR
AYGYADRTSE RVICVLGRKF RSSRALKPPC VTSNTEMFFL FSNFDNGRRN FTTHVMNNQL
NAAFVGQATR AGCAPSYRVK RMDIAKNDEE CVVNAANPRG LPGDGVCKAV YKKWPESFKN
SATPVGTAKT VMCGTYPVIH AVGPNFSNYS ESEGDRELAA AYREVAKEVT RLGVNSVAIP
LLSTGVYSGG KDRLTQSLNH LFTAMDSTDA DVVIYCRDKE WEKKISEAIQ MRTQVELLDE
HISIDCDVVR VHPDSSLAGR KGYSTTEGAL YSYLEGTRFH QTAVDMAEIY TMWPKQTEAN
EQVCLYALGE SIESIRQKCP VDDADASSPP KTVPCLCRYA MTPERVTRLR MNHVTSIIVC
SSFPLPKYKI EGVQKVKCSK VMLFDHNVPS RVSPREYRPS QESVQEASTT TSLTHSQFDL
SVDGKILPVP SDLDADAPAL EPALDDGAIH TLPSATGNLA AVSDWVMSTV PVAPPRRRRG
RNLTVTCDER EGNITPMASV RFFRAELCPV VQETAETRDT AMSLQAPPST ATELSHPPIS
FGAPSETFPI TFGDFNEGEI ESLSSELLTF GDFLPGEVDD LTDSDWSTCS DTDDELRLDR
AGGYIFSSDT GPGHLQQKSV RQSVLPVNTL EEVHEEKCYP PKLDEAKEQL LLKKLQESAS
MANRSRYQSR KVENMKATII QRLKRGCRLY LMSETPKVPT YRTTYPAPVY SPPINVRLSN
PESAVAACNE FLARNYPTVS SYQITDEYDA YLDMVDGSES CLDRATFNPS KLRSYPKQHA
YHAPSIRSAV PSPFQNTLQN VLAAATKRNC NVTQMRELPT LDSAVFNVEC FKKFACNQEY
WEEFAASPIR ITTENLTTYV TKLKGPKAAA LFAKTHNLLP LQEVPMDRFT VDMKRDVKVT
PGTKHTEERP KVQVIQAAEP LATAYLCGIH RELVRRLNAV LLPNVHTLFD MSAEDFDAII
AAHFKPGDTV LETDIASFDK SQDDSLALTA LMLLEDLGVD HSLLDLIEAA FGEISSCHLP
TGTRFKFGAM MKSGMFLTLF VNTLLNITIA SRVLEDRLTK SACAAFIGDD NIIHGVVSDE
LMAARCATWM NMEVKIIDAV VSQKAPYFCG GFILHDIVTG TACRVADPLK RLFKLGKPLA
AGDEQDEDRR RALADEVVRW QRTGLIDELE KAVYSRYEVQ GISVVVMSMA TFASSRSNFE
KLRGPVVTLY GGPK
