ID   R1A_SARS2               Reviewed;        4405 AA.
AC   P0DTC1;
DT   22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT   22-APR-2020, sequence version 1.
DT   29-MAY-2024, entry version 22.
DE   RecName: Full=Replicase polyprotein 1a;
DE            Short=pp1a;
DE   AltName: Full=ORF1a polyprotein;
DE   Contains:
DE     RecName: Full=Host translation inhibitor nsp1;
DE     AltName: Full=Leader protein;
DE     AltName: Full=Non-structural protein 1;
DE              Short=nsp1;
DE   Contains:
DE     RecName: Full=Non-structural protein 2;
DE              Short=nsp2;
DE     AltName: Full=p65 homolog;
DE   Contains:
DE     RecName: Full=Papain-like protease nsp3 {ECO:0000303|PubMed:32726803};
DE              EC=3.4.19.12 {ECO:0000269|PubMed:32726803};
DE              EC=3.4.22.-;
DE     AltName: Full=Non-structural protein 3;
DE              Short=nsp3;
DE     AltName: Full=PL2-PRO;
DE     AltName: Full=Papain-like proteinase;
DE              Short=PL-PRO;
DE   Contains:
DE     RecName: Full=Non-structural protein 4;
DE              Short=nsp4;
DE   Contains:
DE     RecName: Full=3C-like proteinase nsp5;
DE              Short=3CL-PRO;
DE              Short=3CLp;
DE              EC=3.4.22.69;
DE     AltName: Full=Main protease;
DE              Short=Mpro {ECO:0000303|PubMed:32272481};
DE     AltName: Full=Non-structural protein 5;
DE              Short=nsp5;
DE     AltName: Full=SARS coronavirus main proteinase;
DE   Contains:
DE     RecName: Full=Non-structural protein 6;
DE              Short=nsp6;
DE   Contains:
DE     RecName: Full=Non-structural protein 7;
DE              Short=nsp7;
DE   Contains:
DE     RecName: Full=Non-structural protein 8;
DE              Short=nsp8;
DE   Contains:
DE     RecName: Full=RNA-capping enzyme subunit nsp9;
DE     AltName: Full=Non-structural protein 9;
DE              Short=nsp9;
DE              EC=2.7.7.50 {ECO:0000269|PubMed:35944563};
DE   Contains:
DE     RecName: Full=Non-structural protein 10;
DE              Short=nsp10;
DE     AltName: Full=Growth factor-like peptide;
DE              Short=GFL;
DE   Contains:
DE     RecName: Full=Non-structural protein 11;
DE              Short=nsp11;
OS   Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae;
OC   Betacoronavirus; Sarbecovirus;
OC   Severe acute respiratory syndrome coronavirus.
OX   NCBI_TaxID=2697049;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=32015508; DOI=10.1038/s41586-020-2008-3;
RA   Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Song Z.-G., Hu Y., Tao Z.-W.,
RA   Tian J.-H., Pei Y.-Y., Yuan M.-L., Zhang Y.-L., Dai F.-H., Liu Y.,
RA   Wang Q.-M., Zheng J.-J., Xu L., Holmes E.C., Zhang Y.-Z.;
RT   "A new coronavirus associated with human respiratory disease in China.";
RL   Nature 579:265-269(2020).
RN   [2]
RP   VARIANTS ILE-1001; ASP-1708; THR-2230 AND 3675-SER--PHE-3677 DEL.
RC   STRAIN=20B/501Y.V1, B.1.1.7, VOC-202012/01, and VUI-202012/01;
RX   PubMed=33413740; DOI=10.2807/1560-7917.es.2020.26.1.2002106;
RA   Leung K., Shum M.H., Leung G.M., Lam T.T., Wu J.T.;
RT   "Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-
RT   2 in the United Kingdom, October to November 2020.";
RL   Eurosurveillance 26:0-0(2021).
RN   [3]
RP   FUNCTION (HOST TRANSLATION INHIBITOR NSP1).
RX   PubMed=33479166; DOI=10.1073/pnas.2017715118;
RA   Lapointe C.P., Grosely R., Johnson A.G., Wang J., Fernandez I.S.,
RA   Puglisi J.D.;
RT   "Dynamic competition between SARS-CoV-2 NSP1 and mRNA on the human ribosome
RT   inhibits translation initiation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
RN   [4]
RP   FUNCTION (PAPAIN-LIKE PROTEASE NSP3), AND MUTAGENESIS OF CYS-1674.
RX   PubMed=33727702; DOI=10.1038/s41564-021-00884-1;
RA   Liu G., Lee J.H., Parker Z.M., Acharya D., Chiang J.J., van Gent M.,
RA   Riedl W., Davis-Gardner M.E., Wies E., Chiang C., Gack M.U.;
RT   "ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-
RT   CoV-2 papain-like protease to evade host innate immunity.";
RL   Nat. Microbiol. 6:467-478(2021).
RN   [5]
RP   FUNCTION (2'-O-METHYLTRANSFERASE NSP16), SUBCELLULAR LOCATION
RP   (2'-O-METHYLTRANSFERASE NSP16), FUNCTION (HOST TRANSLATION INHIBITOR NSP1),
RP   FUNCTION(NON-STRUCTURAL PROTEIN 8), FUNCTION (NON-STRUCTURAL PROTEIN 9),
RP   SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 8), AND SUBCELLULAR LOCATION
RP   (NON-STRUCTURAL PROTEIN 9).
RX   PubMed=33080218; DOI=10.1016/j.cell.2020.10.004;
RA   Banerjee A.K., Blanco M.R., Bruce E.A., Honson D.D., Chen L.M., Chow A.,
RA   Bhat P., Ollikainen N., Quinodoz S.A., Loney C., Thai J., Miller Z.D.,
RA   Lin A.E., Schmidt M.M., Stewart D.G., Goldfarb D., De Lorenzo G.,
RA   Rihn S.J., Voorhees R.M., Botten J.W., Majumdar D., Guttman M.;
RT   "SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to
RT   Suppress Host Defenses.";
RL   Cell 183:1325-1339(2020).
RN   [6]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 3), AND SUBCELLULAR LOCATION
RP   (NON-STRUCTURAL PROTEIN 3).
RX   PubMed=32763915; DOI=10.1126/science.abd3629;
RA   Wolff G., Limpens R.W.A.L., Zevenhoven-Dobbe J.C., Laugks U., Zheng S.,
RA   de Jong A.W.M., Koning R.I., Agard D.A., Gruenewald K., Koster A.J.,
RA   Snijder E.J., Barcena M.;
RT   "A molecular pore spans the double membrane of the coronavirus replication
RT   organelle.";
RL   Science 369:1395-1398(2020).
RN   [7]
RP   FUNCTION (RNA-CAPPING ENZYME NSP9), FUNCTION (NON-STRUCTURAL PROTEIN 10),
RP   MUTAGENESIS OF ASN-4141 AND ASN-4142, AND INTERACTION WITH NSP12
RP   (RNA-CAPPING ENZYME NSP9).
RX   PubMed=35944563; DOI=10.1038/s41586-022-05185-z;
RA   Park G.J., Osinski A., Hernandez G., Eitson J.L., Majumdar A., Tonelli M.,
RA   Henzler-Wildman K., Pawlowski K., Chen Z., Li Y., Schoggins J.W.,
RA   Tagliabracci V.S.;
RT   "The mechanism of RNA capping by SARS-CoV-2.";
RL   Nature 0:0-0(2022).
RN   [8]
RP   REVIEW, SUBUNIT (NON-STRUCTURAL PROTEIN 7), AND SUBUNIT (NON-STRUCTURAL
RP   PROTEIN 8).
RX   PubMed=34562452; DOI=10.1016/j.jbc.2021.101218;
RA   Perry J.K., Appleby T.C., Bilello J.P., Feng J.Y., Schmitz U.,
RA   Campbell E.A.;
RT   "An atomistic model of the coronavirus replication-transcription complex as
RT   a hexamer assembled around nsp15.";
RL   J. Biol. Chem. 297:101218-101218(2021).
RN   [9]
RP   FUNCTION (3C-LIKE PROTEINASE NSP5), AND MUTAGENESIS OF CYS-3408.
RX   PubMed=35594856; DOI=10.1016/j.molcel.2022.04.033;
RG   COVID Human Genetic Effort;
RA   Planes R., Pinilla M., Santoni K., Hessel A., Passemar C., Lay K.,
RA   Paillette P., Valadao A.C., Robinson K.S., Bastard P., Lam N., Fadrique R.,
RA   Rossi I., Pericat D., Bagayoko S., Leon-Icaza S.A., Rombouts Y.,
RA   Perouzel E., Tiraby M., Zhang Q., Cicuta P., Jouanguy E., Neyrolles O.,
RA   Bryant C.E., Floto A.R., Goujon C., Lei F.Z., Martin-Blondel G., Silva S.,
RA   Casanova J.L., Cougoule C., Reversade B., Marcoux J., Ravet E., Meunier E.;
RT   "Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung
RT   epithelial cells.";
RL   Mol. Cell 82:2385-2400(2022).
RN   [10]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 6), FUNCTION (NON-STRUCTURAL PROTEIN 3),
RP   FUNCTION (NON-STRUCTURAL PROTEIN 4), SUBCELLULAR LOCATION (NON-STRUCTURAL
RP   PROTEIN 6), SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 3), SUBCELLULAR
RP   LOCATION (NON-STRUCTURAL PROTEIN 4), MUTAGENESIS OF 3675-SER--PHE-3677;
RP   PHE-3789 AND THR-3791, ACTIVITY REGULATION (NON-STRUCTURAL PROTEIN 6), AND
RP   INTERACTION WITH HOST ZFYVE1 (NON-STRUCTURAL PROTEIN 6).
RX   PubMed=35551511; DOI=10.1038/s41586-022-04835-6;
RA   Ricciardi S., Guarino A.M., Giaquinto L., Polishchuk E.V., Santoro M.,
RA   Di Tullio G., Wilson C., Panariello F., Soares V.C., Dias S.S.G.,
RA   Santos J.C., Souza T.M.L., Fusco G., Viscardi M., Brandi S., Bozza P.T.,
RA   Polishchuk R.S., Venditti R., De Matteis M.A.;
RT   "The role of NSP6 in the biogenesis of the SARS-CoV-2 replication
RT   organelle.";
RL   Nature 606:761-768(2022).
RN   [11]
RP   FUNCTION (HOST TRANSLATION INHIBITOR NSP1).
RX   PubMed=36534661; DOI=10.1371/journal.ppat.1011041;
RA   Dolliver S.M., Kleer M., Bui-Marinos M.P., Ying S., Corcoran J.A.,
RA   Khaperskyy D.A.;
RT   "Nsp1 proteins of human coronaviruses HCoV-OC43 and SARS-CoV2 inhibit
RT   stress granule formation.";
RL   PLoS Pathog. 18:e1011041-e1011041(2022).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.16 ANGSTROMS) OF 3C-LIKE PROTEINASE NSP5 AND IN
RP   COMPLEX WITH MICHAEL ACCEPTOR INHIBITOR N3.
RA   Liu X., Zhang B., Jin Z., Yang H., Rao Z.;
RT   "The crystal structure of 2019-nCoV main protease in complex with an
RT   inhibitor N3.";
RL   Submitted (FEB-2020) to the PDB data bank.
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 3C-LIKE PROTEINASE NSP5 IN
RP   COMPLEX WITH ALPHA-KETOAMIDE INHIBITORS, SUBUNIT (3C-LIKE PROTEINASE NSP5),
RP   ACTIVE SITE, AND ACTIVITY REGULATION.
RX   PubMed=32198291; DOI=10.1126/science.abb3405;
RA   Zhang L., Lin D., Sun X., Curth U., Drosten C., Sauerhering L., Becker S.,
RA   Rox K., Hilgenfeld R.;
RT   "Crystal structure of SARS-CoV-2 main protease provides a basis for design
RT   of improved alpha-ketoamide inhibitors.";
RL   Science 368:409-412(2020).
RN   [14]
RP   X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 3C-LIKE PROTEINASE APOENZYME AND
RP   IN COMPLEX WITH MICHAEL ACCEPTOR INHIBITOR N3, FUNCTION (3C-LIKE PROTEINASE
RP   NSP5), AND CATALYTIC ACTIVITY (3C-LIKE PROTEINASE NSP5).
RX   PubMed=32272481; DOI=10.1038/s41586-020-2223-y;
RA   Jin Z., Du X., Xu Y., Deng Y., Liu M., Zhao Y., Zhang B., Li X., Zhang L.,
RA   Peng C., Duan Y., Yu J., Wang L., Yang K., Liu F., Jiang R., Yang X.,
RA   You T., Liu X., Yang X., Bai F., Liu H., Liu X., Guddat L.W., Xu W.,
RA   Xiao G., Qin C., Shi Z., Jiang H., Rao Z., Yang H.;
RT   "Structure of Mpro from COVID-19 virus and discovery of its inhibitors.";
RL   Nature 582:289-293(2020).
RN   [15]
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.9 ANGSTROMS) OF NON-STRUCTURAL PROTEIN
RP   7 AND NON-STRUCTURAL PROTEIN 8, SUBUNIT (NON-STRUCTURAL PROTEIN 7), SUBUNIT
RP   (NON-STRUCTURAL PROTEIN 8), FUNCTION (NON-STRUCTURAL PROTEIN 7), AND
RP   FUNCTION (NON-STRUCTURAL PROTEIN 8).
RX   PubMed=32277040; DOI=10.1126/science.abb7498;
RA   Gao Y., Yan L., Huang Y., Liu F., Zhao Y., Cao L., Wang T., Sun Q.,
RA   Ming Z., Zhang L., Ge J., Zheng L., Zhang Y., Wang H., Zhu Y., Zhu C.,
RA   Hu T., Hua T., Zhang B., Yang X., Li J., Yang H., Liu Z., Xu W.,
RA   Guddat L.W., Wang Q., Lou Z., Rao Z.;
RT   "Structure of the RNA-dependent RNA polymerase from COVID-19 virus.";
RL   Science 368:779-782(2020).
RN   [16]
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.5 ANGSTROMS) OF NON-STRUCTURAL PROTEIN
RP   7 AND NON-STRUCTURAL PROTEIN 8, SUBUNIT (NON-STRUCTURAL PROTEIN 7), SUBUNIT
RP   (NON-STRUCTURAL PROTEIN 8), FUNCTION (NON-STRUCTURAL PROTEIN 7), AND
RP   FUNCTION (NON-STRUCTURAL PROTEIN 8).
RX   PubMed=32358203; DOI=10.1126/science.abc1560;
RA   Yin W., Mao C., Luan X., Shen D.D., Shen Q., Su H., Wang X., Zhou F.,
RA   Zhao W., Gao M., Chang S., Xie Y.C., Tian G., Jiang H.W., Tao S.C.,
RA   Shen J., Jiang Y., Jiang H., Xu Y., Zhang S., Zhang Y., Xu H.E.;
RT   "Structural basis for inhibition of the RNA-dependent RNA polymerase from
RT   SARS-CoV-2 by remdesivir.";
RL   Science 368:1499-1504(2020).
RN   [17]
RP   X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 3C-LIKE PROTEINASE NSP5 IN COMPLEX
RP   WITH COMPOUND 11A AND COMPOUND 11B, FUNCTION (3C-LIKE PROTEINASE NSP5),
RP   CATALYTIC ACTIVITY (3C-LIKE PROTEINASE NSP5), AND ACTIVITY REGULATION
RP   (3C-LIKE PROTEINASE NSP5).
RX   PubMed=32321856; DOI=10.1126/science.abb4489;
RA   Dai W., Zhang B., Su H., Li J., Zhao Y., Xie X., Jin Z., Liu F., Li C.,
RA   Li Y., Bai F., Wang H., Cheng X., Cen X., Hu S., Yang X., Wang J., Liu X.,
RA   Xiao G., Jiang H., Rao Z., Zhang L.K., Xu Y., Yang H., Liu H.;
RT   "Structure-based design of antiviral drug candidates targeting the SARS-
RT   CoV-2 main protease.";
RL   Science 368:1331-1335(2020).
RN   [18]
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.9 ANGSTROMS) OF NON-STRUCTURAL PROTEIN
RP   7 AND NON-STRUCTURAL PROTEIN 8, SUBUNIT (NON-STRUCTURAL PROTEIN 7), SUBUNIT
RP   (NON-STRUCTURAL PROTEIN 8), FUNCTION (NON-STRUCTURAL PROTEIN 7), AND
RP   FUNCTION (NON-STRUCTURAL PROTEIN 8).
RX   PubMed=32438371; DOI=10.1038/s41586-020-2368-8;
RA   Hillen H.S., Kokic G., Farnung L., Dienemann C., Tegunov D., Cramer P.;
RT   "Structure of replicating SARS-CoV-2 polymerase.";
RL   Nature 584:154-156(2020).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (0.95 ANGSTROMS) OF NON-STRUCTURAL PROTEIN 3 MACRO
RP   DOMAIN, AND FUNCTION OF NON-STRUCTURAL PROTEIN 3.
RX   PubMed=32578982; DOI=10.1021/acs.biochem.0c00309;
RA   Frick D.N., Virdi R.S., Vuksanovic N., Dahal N., Silvaggi N.R.;
RT   "Molecular Basis for ADP-ribose Binding to the Mac1 Domain of SARS-CoV-2
RT   Nsp3.";
RL   Biochemistry 59:2608-2615(2020).
RN   [20]
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.93 ANGSTROMS) OF NON-STRUCTURAL PROTEIN
RP   7 AND NON-STRUCTURAL PROTEIN 8 IN COMPLEX WITH ZINC ION, SUBUNIT
RP   (NON-STRUCTURAL PROTEIN 7), SUBUNIT (NON-STRUCTURAL PROTEIN 8), FUNCTION
RP   (NON-STRUCTURAL PROTEIN 7), AND FUNCTION (NON-STRUCTURAL PROTEIN 8).
RX   PubMed=32526208; DOI=10.1016/j.cell.2020.05.034;
RA   Wang Q., Wu J., Wang H., Gao Y., Liu Q., Mu A., Ji W., Yan L., Zhu Y.,
RA   Zhu C., Fang X., Yang X., Huang Y., Gao H., Liu F., Ge J., Sun Q., Yang X.,
RA   Xu W., Liu Z., Yang H., Lou Z., Jiang B., Guddat L.W., Gong P., Rao Z.;
RT   "Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase.";
RL   Cell 182:417-428(2020).
RN   [21]
RP   X-RAY CRYSTALLOGRAPHY (3.18 ANGSTROMS) OF NON-STRUCTURAL PROTEIN 3,
RP   FUNCTION (NON-STRUCTURAL PROTEIN 3), CATALYTIC ACTIVITY (NON-STRUCTURAL
RP   PROTEIN 3), ACTIVITY REGULATION (NON-STRUCTURAL PROTEIN 3), AND MUTAGENESIS
RP   OF VAL-1629; PHE-1632; THR-1638; CYS-1674 AND TYR-1831.
RX   PubMed=32726803; DOI=10.1038/s41586-020-2601-5;
RA   Shin D., Mukherjee R., Grewe D., Bojkova D., Baek K., Bhattacharya A.,
RA   Schulz L., Widera M., Mehdipour A.R., Tascher G., Geurink P.P., Wilhelm A.,
RA   van der Heden van Noort G.J., Ovaa H., Mueller S., Knobeloch K.P.,
RA   Rajalingam K., Schulman B.A., Cinatl J., Hummer G., Ciesek S., Dikic I.;
RT   "Papain-like protease regulates SARS-CoV-2 viral spread and innate
RT   immunity.";
RL   Nature 587:657-662(2020).
RN   [22]
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.6 ANGSTROMS) OF NON-STRUCTURAL PROTEIN
RP   1, FUNCTION (NON-STRUCTURAL PROTEIN 1), AND MUTAGENESIS OF LYS-164 AND
RP   HIS-165.
RX   PubMed=32680882; DOI=10.1126/science.abc8665;
RA   Thoms M., Buschauer R., Ameismeier M., Koepke L., Denk T.,
RA   Hirschenberger M., Kratzat H., Hayn M., Mackens-Kiani T., Cheng J.,
RA   Straub J.H., Stuerzel C.M., Froehlich T., Berninghausen O., Becker T.,
RA   Kirchhoff F., Sparrer K.M.J., Beckmann R.;
RT   "Structural basis for translational shutdown and immune evasion by the Nsp1
RT   protein of SARS-CoV-2.";
RL   Science 369:1249-1255(2020).
RN   [23]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 1).
RX   PubMed=32733001; DOI=10.1038/s41467-020-17665-9;
RA   Lei X., Dong X., Ma R., Wang W., Xiao X., Tian Z., Wang C., Wang Y., Li L.,
RA   Ren L., Guo F., Zhao Z., Zhou Z., Xiang Z., Wang J.;
RT   "Activation and evasion of type I interferon responses by SARS-CoV-2.";
RL   Nat. Commun. 11:3810-3810(2020).
RN   [24]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 1), FUNCTION (NON-STRUCTURAL PROTEIN 6),
RP   AND INTERACTION WITH HOST TBK1 (NON-STRUCTURAL PROTEIN 6).
RX   PubMed=32979938; DOI=10.1016/j.celrep.2020.108234;
RA   Xia H., Cao Z., Xie X., Zhang X., Chen J.Y., Wang H., Menachery V.D.,
RA   Rajsbaum R., Shi P.Y.;
RT   "Evasion of Type I Interferon by SARS-CoV-2.";
RL   Cell Rep. 33:108234-108234(2020).
RN   [25]
RP   SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 1), SUBCELLULAR LOCATION
RP   (NON-STRUCTURAL PROTEIN 2), SUBCELLULAR LOCATION (3C-LIKE PROTEINASE),
RP   SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 7), SUBCELLULAR LOCATION
RP   (NON-STRUCTURAL PROTEIN 8), SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN
RP   9), AND SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 10).
RX   PubMed=33060197; DOI=10.1126/science.abe9403;
RG   QCRG Structural Biology Consortium;
RG   Zoonomia Consortium;
RA   Gordon D.E., Hiatt J., Bouhaddou M., Rezelj V.V., Ulferts S., Braberg H.,
RA   Jureka A.S., Obernier K., Guo J.Z., Batra J., Kaake R.M., Weckstein A.R.,
RA   Owens T.W., Gupta M., Pourmal S., Titus E.W., Cakir M., Soucheray M.,
RA   McGregor M., Cakir Z., Jang G., O'Meara M.J., Tummino T.A., Zhang Z.,
RA   Foussard H., Rojc A., Zhou Y., Kuchenov D., Huettenhain R., Xu J.,
RA   Eckhardt M., Swaney D.L., Fabius J.M., Ummadi M., Tutuncuoglu B.,
RA   Rathore U., Modak M., Haas P., Haas K.M., Naing Z.Z.C., Pulido E.H.,
RA   Shi Y., Barrio-Hernandez I., Memon D., Petsalaki E., Dunham A.,
RA   Marrero M.C., Burke D., Koh C., Vallet T., Silvas J.A., Azumaya C.M.,
RA   Billesboelle C., Brilot A.F., Campbell M.G., Diallo A., Dickinson M.S.,
RA   Diwanji D., Herrera N., Hoppe N., Kratochvil H.T., Liu Y., Merz G.E.,
RA   Moritz M., Nguyen H.C., Nowotny C., Puchades C., Rizo A.N.,
RA   Schulze-Gahmen U., Smith A.M., Sun M., Young I.D., Zhao J., Asarnow D.,
RA   Biel J., Bowen A., Braxton J.R., Chen J., Chio C.M., Chio U.S.,
RA   Deshpande I., Doan L., Faust B., Flores S., Jin M., Kim K., Lam V.L.,
RA   Li F., Li J., Li Y.L., Li Y., Liu X., Lo M., Lopez K.E., Melo A.A.,
RA   Moss F.R. III, Nguyen P., Paulino J., Pawar K.I., Peters J.K.,
RA   Pospiech T.H. Jr., Safari M., Sangwan S., Schaefer K., Thomas P.V.,
RA   Thwin A.C., Trenker R., Tse E., Tsui T.K.M., Wang F., Whitis N., Yu Z.,
RA   Zhang K., Zhang Y., Zhou F., Saltzberg D., Hodder A.J., Shun-Shion A.S.,
RA   Williams D.M., White K.M., Rosales R., Kehrer T., Miorin L., Moreno E.,
RA   Patel A.H., Rihn S., Khalid M.M., Vallejo-Gracia A., Fozouni P.,
RA   Simoneau C.R., Roth T.L., Wu D., Karim M.A., Ghoussaini M., Dunham I.,
RA   Berardi F., Weigang S., Chazal M., Park J., Logue J., McGrath M.,
RA   Weston S., Haupt R., Hastie C.J., Elliott M., Brown F., Burness K.A.,
RA   Reid E., Dorward M., Johnson C., Wilkinson S.G., Geyer A., Giesel D.M.,
RA   Baillie C., Raggett S., Leech H., Toth R., Goodman N., Keough K.C.,
RA   Lind A.L., Klesh R.J., Hemphill K.R., Carlson-Stevermer J., Oki J.,
RA   Holden K., Maures T., Pollard K.S., Sali A., Agard D.A., Cheng Y.,
RA   Fraser J.S., Frost A., Jura N., Kortemme T., Manglik A., Southworth D.R.,
RA   Stroud R.M., Alessi D.R., Davies P., Frieman M.B., Ideker T., Abate C.,
RA   Jouvenet N., Kochs G., Shoichet B., Ott M., Palmarini M., Shokat K.M.,
RA   Garcia-Sastre A., Rassen J.A., Grosse R., Rosenberg O.S., Verba K.A.,
RA   Basler C.F., Vignuzzi M., Peden A.A., Beltrao P., Krogan N.J.;
RT   "Comparative host-coronavirus protein interaction networks reveal pan-viral
RT   disease mechanisms.";
RL   Science 0:0-0(2020).
RN   [26]
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.8 ANGSTROMS) OF NON-STRUCTURAL PROTEIN
RP   1, FUNCTION (NON-STRUCTURAL PROTEIN 1), AND MUTAGENESIS OF
RP   154-TYR--PHE-157; 164-LYS-HIS-165 AND 171-ARG--ARG-175.
RX   PubMed=32908316; DOI=10.1038/s41594-020-0511-8;
RA   Schubert K., Karousis E.D., Jomaa A., Scaiola A., Echeverria B.,
RA   Gurzeler L.A., Leibundgut M., Thiel V., Muehlemann O., Ban N.;
RT   "SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation.";
RL   Nat. Struct. Mol. Biol. 27:959-966(2020).
RN   [27]
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.3 ANGSTROMS) OF NON-STRUCTURAL PROTEIN
RP   7; NON-STRUCTURAL PROTEIN 8; NON-STRUCTURAL PROTEIN 9 AND NON-STRUCTURAL
RP   PROTEIN 10, AND SUBUNIT (NON-STRUCTURAL PROTEIN 8).
RX   PubMed=33232691; DOI=10.1016/j.cell.2020.11.016;
RA   Yan L., Ge J., Zheng L., Zhang Y., Gao Y., Wang T., Huang Y., Yang Y.,
RA   Gao S., Li M., Liu Z., Wang H., Li Y., Chen Y., Guddat L.W., Wang Q.,
RA   Rao Z., Lou Z.;
RT   "Cryo-EM Structure of an Extended SARS-CoV-2 Replication and Transcription
RT   Complex Reveals an Intermediate State in Cap Synthesis.";
RL   Cell 184:184-193(2021).
RN   [28]
RP   STRUCTURE BY NMR OF 834-929 (PAPAIN-LIKE PROTEASE NSP3), AND INTERACTION
RP   WITH N (PAPAIN-LIKE PROTEASE NSP3).
RX   PubMed=35044811; DOI=10.1126/sciadv.abm4034;
RA   Bessa L.M., Guseva S., Camacho-Zarco A.R., Salvi N., Maurin D., Perez L.M.,
RA   Botova M., Malki A., Nanao M., Jensen M.R., Ruigrok R.W.H., Blackledge M.;
RT   "The intrinsically disordered SARS-CoV-2 nucleoprotein in dynamic complex
RT   with its viral partner nsp3a.";
RL   Sci. Adv. 8:4034-4034(2022).
RN   [29]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 2), INTERACTION WITH HOST GIGYF2
RP   (NON-STRUCTURAL PROTEIN 2), SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP   GLY-442.
RX   PubMed=35878012; DOI=10.1073/pnas.2204539119;
RA   Xu Z., Choi J.H., Dai D.L., Luo J., Ladak R.J., Li Q., Wang Y., Zhang C.,
RA   Wiebe S., Liu A.C.H., Ran X., Yang J., Naeli P., Garzia A., Zhou L.,
RA   Mahmood N., Deng Q., Elaish M., Lin R., Mahal L.K., Hobman T.C.,
RA   Pelletier J., Alain T., Vidal S.M., Duchaine T., Mazhab-Jafari M.T.,
RA   Mao X., Jafarnejad S.M., Sonenberg N.;
RT   "SARS-CoV-2 impairs interferon production via NSP2-induced repression of
RT   mRNA translation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 119:e2204539119-e2204539119(2022).
CC   -!- FUNCTION: [Replicase polyprotein 1a]: Multifunctional protein involved
CC       in the transcription and replication of viral RNAs. Contains the
CC       proteinases responsible for the cleavages of the polyprotein.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Host translation inhibitor nsp1]: Inhibits host translation
CC       by associating with the open head conformation of the 40S subunit
CC       (PubMed:32680882, PubMed:32908316, PubMed:33080218, PubMed:33479166).
CC       The C-terminus binds to and obstructs ribosomal mRNA entry tunnel
CC       (PubMed:32680882, PubMed:32908316, PubMed:33080218, PubMed:33479166).
CC       Thereby inhibits antiviral response triggered by innate immunity or
CC       interferons (PubMed:32680882, PubMed:32979938, PubMed:33080218). The
CC       nsp1-40S ribosome complex further induces an endonucleolytic cleavage
CC       near the 5'UTR of host mRNAs, targeting them for degradation (By
CC       similarity). This inhibits the integrated stress response (ISR) in the
CC       infected cell by preventing EIF2S1/eIF2-alpha phosphorylation upstream
CC       of stress granule formation and depletes host G3BP1 (PubMed:36534661).
CC       Viral mRNAs less susceptible to nsp1-mediated inhibition of
CC       translation, because of their 5'-end leader sequence (PubMed:32908316,
CC       PubMed:33080218). {ECO:0000250|UniProtKB:P0C6X7,
CC       ECO:0000269|PubMed:32680882, ECO:0000269|PubMed:32908316,
CC       ECO:0000269|PubMed:32979938, ECO:0000269|PubMed:33080218,
CC       ECO:0000269|PubMed:33479166, ECO:0000269|PubMed:36534661}.
CC   -!- FUNCTION: [Non-structural protein 2]: Enhances mRNA repression of the
CC       4EHP-GYF2 complex in the host, thereby inhibiting the antiviral
CC       response and facilitating SARS-CoV-2 replication. Possibly acts in
CC       cooperation with nsp1, which induces ribosome stalling on host mRNA,
CC       triggering mRNA repression by the host 4EHP-GYF2 complex which is
CC       enhanced by nsp2. {ECO:0000269|PubMed:35878012}.
CC   -!- FUNCTION: [Papain-like protease nsp3]: Responsible for the cleavages
CC       located at the N-terminus of the replicase polyprotein. Participates
CC       together with nsp4 in the assembly of virally-induced cytoplasmic
CC       double-membrane vesicles necessary for viral replication
CC       (PubMed:35551511). Antagonizes innate immune induction of type I
CC       interferon by blocking the phosphorylation, dimerization and subsequent
CC       nuclear translocation of host IRF3 (PubMed:32733001). Prevents also
CC       host NF-kappa-B signaling (By similarity). In addition, PL-PRO
CC       possesses a deubiquitinating/deISGylating activity and processes both
CC       'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular
CC       substrates (PubMed:32726803). Cleaves preferentially ISG15 from
CC       antiviral protein IFIH1 (MDA5), but not RIGI (PubMed:33727702). Can
CC       play a role in host ADP-ribosylation by ADP-ribose (PubMed:32578982).
CC       Plays a role in the formation and maintenance of double membrane
CC       vesicles (DMVs) replication organelles (PubMed:35551511). DMVs are
CC       formed by nsp3 and nsp4, while nsp6 zippers ER membranes and connects
CC       to lipid droplets (PubMed:35551511). {ECO:0000250|UniProtKB:P0C6X7,
CC       ECO:0000269|PubMed:32578982, ECO:0000269|PubMed:32726803,
CC       ECO:0000269|PubMed:32733001, ECO:0000269|PubMed:33727702,
CC       ECO:0000269|PubMed:35551511}.
CC   -!- FUNCTION: [Non-structural protein 4]: Plays a role in the formation and
CC       maintenance of double membrane vesicles (DMVs) replication organelles
CC       (PubMed:35551511). DMVs are formed by nsp3 and nsp4, while nsp6 zippers
CC       ER membranes and connects to lipid droplets (PubMed:35551511).
CC       {ECO:0000269|PubMed:35551511}.
CC   -!- FUNCTION: [3C-like proteinase nsp5]: Cleaves the C-terminus of
CC       replicase polyprotein at 11 sites (PubMed:32321856). Recognizes
CC       substrates containing the core sequence [ILMVF]-Q-|-[SGACN]
CC       (PubMed:32198291, PubMed:32272481). May cleave human NLRP1 in lung
CC       epithelial cells, thereby activating the NLRP1 inflammasome pathway
CC       (PubMed:35594856). May cleave human GSDMD, triggering alternative
CC       GSDME-mediated epithelial cell death upon activation of the NLRP1
CC       inflammasome, which may enhance the release interleukins 1B, 6, 16 and
CC       18 (PubMed:35594856). Also able to bind an ADP-ribose-1''-phosphate
CC       (ADRP) (PubMed:32198291, PubMed:32272481).
CC       {ECO:0000269|PubMed:32198291, ECO:0000269|PubMed:32272481,
CC       ECO:0000269|PubMed:32321856, ECO:0000269|PubMed:32680882,
CC       ECO:0000269|PubMed:35594856}.
CC   -!- FUNCTION: [Non-structural protein 6]: Plays a role in the formation and
CC       maintenance of double membrane vesicles (DMVs) replication organelles
CC       (PubMed:35551511). DMVs are formed by nsp3 and nsp4, while nsp6 zippers
CC       ER membranes and connects to lipid droplets (LDs) (PubMed:35551511).
CC       LDs are consumed during DMV formation (PubMed:35551511). Binds to host
CC       TBK1 without affecting TBK1 phosphorylation; the interaction with TBK1
CC       decreases IRF3 phosphorylation, which leads to reduced IFN-beta
CC       production (PubMed:32979938). {ECO:0000269|PubMed:32979938,
CC       ECO:0000269|PubMed:35551511}.
CC   -!- FUNCTION: [Non-structural protein 7]: Plays a role in viral RNA
CC       synthesis (PubMed:32277040, PubMed:32358203, PubMed:32438371,
CC       PubMed:32526208). Forms a hexadecamer with nsp8 (8 subunits of each)
CC       that may participate in viral replication by acting as a primase.
CC       Alternatively, may synthesize substantially longer products than
CC       oligonucleotide primers (By similarity). {ECO:0000250|UniProtKB:P0C6X7,
CC       ECO:0000269|PubMed:32277040, ECO:0000269|PubMed:32358203,
CC       ECO:0000269|PubMed:32438371, ECO:0000269|PubMed:32526208}.
CC   -!- FUNCTION: [Non-structural protein 8]: Plays a role in viral RNA
CC       synthesis (PubMed:32277040, PubMed:32358203, PubMed:32438371,
CC       PubMed:32526208). Forms a hexadecamer with nsp7 (8 subunits of each)
CC       that may participate in viral replication by acting as a primase.
CC       Alternatively, may synthesize substantially longer products than
CC       oligonucleotide primers (By similarity). Interacts with ribosome signal
CC       recognition particle RNA (SRP) (PubMed:33080218). Together with NSP9,
CC       suppress protein integration into the cell membrane, thereby disrupting
CC       host immune defenses (PubMed:33080218). {ECO:0000250|UniProtKB:P0C6X7,
CC       ECO:0000269|PubMed:32277040, ECO:0000269|PubMed:32358203,
CC       ECO:0000269|PubMed:32438371, ECO:0000269|PubMed:32526208,
CC       ECO:0000269|PubMed:33080218}.
CC   -!- FUNCTION: [RNA-capping enzyme subunit nsp9]: Catalytic subunit of viral
CC       RNA capping enzyme which catalyzes the RNA guanylyltransferase reaction
CC       for genomic and sub-genomic RNAs (PubMed:35944563). The kinase-like
CC       NiRAN domain of NSP12 transfers RNA to the amino terminus of NSP9,
CC       forming a covalent RNA-protein intermediate (PubMed:35944563).
CC       Subsequently, the NiRAN domain transfers RNA to GDP, forming the core
CC       cap structure GpppA-RNA (PubMed:35944563). The NSP14 and NSP16
CC       methyltransferases then add methyl groups to form functional cap
CC       structures (PubMed:35944563). Interacts with ribosome signal
CC       recognition particle RNA (SRP) (PubMed:33080218). Together with NSP8,
CC       suppress protein integration into the cell membrane, thereby disrupting
CC       host immune defenses (PubMed:33080218). {ECO:0000269|PubMed:33080218,
CC       ECO:0000269|PubMed:35944563}.
CC   -!- FUNCTION: [Non-structural protein 10]: Plays a pivotal role in viral
CC       transcription by stimulating both nsp14 3'-5' exoribonuclease (By
CC       similarity) and nsp16 2'-O-methyltransferase activities
CC       (PubMed:35944563). Therefore plays an essential role in viral mRNAs cap
CC       methylation. {ECO:0000250|UniProtKB:P0C6X7,
CC       ECO:0000269|PubMed:35944563}.
CC   -!- CATALYTIC ACTIVITY: [Papain-like protease nsp3]:
CC       Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC         and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC         residue protein attached to proteins as an intracellular targeting
CC         signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:32726803};
CC   -!- CATALYTIC ACTIVITY: [3C-like proteinase nsp5]:
CC       Reaction=TSAVLQ-|-SGFRK-NH2 and SGVTFQ-|-GKFKK the two peptides
CC         corresponding to the two self-cleavage sites of the SARS 3C-like
CC         proteinase are the two most reactive peptide substrates. The enzyme
CC         exhibits a strong preference for substrates containing Gln at P1
CC         position and Leu at P2 position.; EC=3.4.22.69;
CC         Evidence={ECO:0000269|PubMed:32198291, ECO:0000269|PubMed:32272481,
CC         ECO:0000269|PubMed:32321856};
CC   -!- CATALYTIC ACTIVITY: [RNA-capping enzyme subunit nsp9]:
CC       Reaction=a 5'-end diphospho-ribonucleoside in mRNA + GTP + H(+) = a 5'-
CC         end (5'-triphosphoguanosine)-ribonucleoside in mRNA + diphosphate;
CC         Xref=Rhea:RHEA:67012, Rhea:RHEA-COMP:17165, Rhea:RHEA-COMP:17166,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565,
CC         ChEBI:CHEBI:167616, ChEBI:CHEBI:167617; EC=2.7.7.50;
CC         Evidence={ECO:0000269|PubMed:35944563};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:67014;
CC         Evidence={ECO:0000269|PubMed:35944563};
CC   -!- ACTIVITY REGULATION: [Non-structural protein 6]: Inhibited ex vivo by
CC       K22. It may shift NSP6 zippering activity towards the nuclear envelope,
CC       thereby impairing formation of the NSP6-compartment necessary for viral
CC       transcription/replication. {ECO:0000269|PubMed:35551511}.
CC   -!- ACTIVITY REGULATION: [Papain-like protease nsp3]: Inhibited in vitro by
CC       GRL-0617. {ECO:0000269|PubMed:32726803}.
CC   -!- ACTIVITY REGULATION: [3C-like proteinase nsp5]: Inhibited by pyridone-
CC       containing alpha-ketoamides compounds 13a and 13b. In turn, alpha-
CC       ketoamide 13b (tert-butyl (1-((S)-1-(((S)-4-(benzylamino)-3,4-dioxo-1-
CC       ((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclopropyl-1-oxopropan-
CC       2-yl)-2-oxo-1,2-dihydropyridin-3-yl)carbamate) inhibits SARS-CoV-2
CC       replication in human lung cells (PubMed:32198291). Inhibited ex vivo by
CC       michael acceptor inhibitor N3 (PubMed:32272481). Inhibited ex vivo by
CC       compound 11a and 11b (PubMed:32321856). {ECO:0000269|PubMed:32198291,
CC       ECO:0000269|PubMed:32272481, ECO:0000269|PubMed:32321856}.
CC   -!- SUBUNIT: [Non-structural protein 2]: Interacts with host PHB and PHB2.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBUNIT: [Papain-like protease nsp3]: May form homohexamers
CC       (PubMed:32763915). Interacts with N protein (PubMed:35044811).
CC       {ECO:0000269|PubMed:32763915, ECO:0000269|PubMed:35044811}.
CC   -!- SUBUNIT: [3C-like proteinase nsp5]: 3CL-PRO exists as monomer and
CC       homodimer. Only the homodimer shows catalytic activity.
CC       {ECO:0000269|PubMed:32198291}.
CC   -!- SUBUNIT: [Non-structural protein 4]: Interacts with PL-PRO and nsp6.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBUNIT: [Non-structural protein 6]: Forms homodimers
CC       (PubMed:35551511). Interacts with host ZFYVE1 (DFCP1)
CC       (PubMed:35551511), which leads to ER and DMVs binding to lipid
CC       droplets. Interacts with host TBK1; this interaction decreases IRF3
CC       phosphorylation by 57%, which leads to reduced IFN-beta production.
CC       {ECO:0000269|PubMed:32979938, ECO:0000269|PubMed:35551511}.
CC   -!- SUBUNIT: [Non-structural protein 7]: Interacts with nsp8 and nsp12 to
CC       form the replication-transcription complex (RTC): nsp12, nsp7, two
CC       subunits of nsp8, and up to two subunits of nsp13 (PubMed:32277040,
CC       PubMed:32358203, PubMed:32438371, PubMed:32526208, PubMed:34562452).
CC       Eight copies of nsp7 and eight copies of nsp8 assemble to form a
CC       heterohexadecamer dsRNA-encircling ring structure (By similarity).
CC       {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:32277040,
CC       ECO:0000269|PubMed:32358203, ECO:0000269|PubMed:32438371,
CC       ECO:0000269|PubMed:32526208, ECO:0000305|PubMed:34562452}.
CC   -!- SUBUNIT: [Non-structural protein 8]: Interacts with nsp7, nsp13 and
CC       nsp12 (PubMed:33232691) to form the replication-transcription complex
CC       (RTC): nsp12, nsp7, two subunits of nsp8, and up to two subunits of
CC       nsp13 (PubMed:32277040, PubMed:32358203, PubMed:32438371,
CC       PubMed:32526208, PubMed:34562452). Eight copies of nsp7 and eight
CC       copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling
CC       ring structure (By similarity). {ECO:0000250|UniProtKB:P0C6X7,
CC       ECO:0000269|PubMed:32277040, ECO:0000269|PubMed:32358203,
CC       ECO:0000269|PubMed:32438371, ECO:0000269|PubMed:32526208,
CC       ECO:0000269|PubMed:33232691, ECO:0000305|PubMed:34562452}.
CC   -!- SUBUNIT: [RNA-capping enzyme subunit nsp9]: Is a dimer (By similarity).
CC       Interacts with NSP12 (PubMed:35944563). {ECO:0000250|UniProtKB:P0C6X7,
CC       ECO:0000269|PubMed:35944563}.
CC   -!- SUBUNIT: [Non-structural protein 10]: Forms a dodecamer and interacts
CC       with nsp14 and nsp16; these interactions enhance nsp14 and nsp16
CC       enzymatic activities. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- INTERACTION:
CC       PRO_0000449645; O75347: TBCA; Xeno; NbExp=2; IntAct=EBI-25475882, EBI-2686341;
CC   -!- SUBCELLULAR LOCATION: [Host translation inhibitor nsp1]: Host cytoplasm
CC       {ECO:0000269|PubMed:33060197}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 2]: Host cytoplasm
CC       {ECO:0000269|PubMed:33060197}. Host endosome
CC       {ECO:0000269|PubMed:33060197}.
CC   -!- SUBCELLULAR LOCATION: [Papain-like protease nsp3]: Host endoplasmic
CC       reticulum membrane; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:35551511}. Note=Localizes in virally-induced
CC       cytoplasmic double-membrane vesicles (DMV).
CC       {ECO:0000269|PubMed:35551511}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 4]: Host endoplasmic
CC       reticulum membrane; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:35551511}. Note=Localizes in virally-induced
CC       cytoplasmic double-membrane vesicles (DMV).
CC       {ECO:0000269|PubMed:35551511}.
CC   -!- SUBCELLULAR LOCATION: [3C-like proteinase nsp5]: Host cytoplasm
CC       {ECO:0000269|PubMed:33060197}. Host Golgi apparatus
CC       {ECO:0000269|PubMed:33060197}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 6]: Host endoplasmic
CC       reticulum membrane; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:35551511}. Note=Localizes at zppered ER membranes
CC       close to double-membrane vesicles (DMV). {ECO:0000269|PubMed:35551511}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 7]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250|UniProtKB:P0C6X9}. Host cytoplasm
CC       {ECO:0000269|PubMed:33060197}. Host endoplasmic reticulum
CC       {ECO:0000269|PubMed:33060197}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC       localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC       they merge into confluent complexes. {ECO:0000250|UniProtKB:P0C6X9}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 8]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250|UniProtKB:P0C6X9}. Host cytoplasm
CC       {ECO:0000269|PubMed:33060197, ECO:0000269|PubMed:33080218}. Host
CC       endoplasmic reticulum {ECO:0000269|PubMed:33060197}. Note=nsp7, nsp8,
CC       nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear.
CC       Late in infection, they merge into confluent complexes.
CC       {ECO:0000250|UniProtKB:P0C6X9}.
CC   -!- SUBCELLULAR LOCATION: [RNA-capping enzyme subunit nsp9]: Host
CC       cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P0C6X9}. Host
CC       cytoplasm {ECO:0000269|PubMed:33060197, ECO:0000269|PubMed:33080218}.
CC       Host endoplasmic reticulum {ECO:0000269|PubMed:33060197}. Note=nsp7,
CC       nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely
CC       perinuclear. Late in infection, they merge into confluent complexes.
CC       {ECO:0000250|UniProtKB:P0C6X9}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 10]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250|UniProtKB:P0C6X9}. Host cytoplasm
CC       {ECO:0000269|PubMed:33060197}. Host endoplasmic reticulum
CC       {ECO:0000269|PubMed:33060197}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC       localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC       they merge into confluent complexes. {ECO:0000250|UniProtKB:P0C6X9}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Ribosomal frameshifting; Named isoforms=2;
CC         Comment=Normal translation results in Replicase polyprotein 1a.
CC         Ribosomal frameshifting at the end of this protein occurs at low
CC         frequency and produces Replicase polyprotein 1ab.;
CC       Name=Replicase polyprotein 1a;
CC         IsoId=P0DTC1-1; Sequence=Displayed;
CC       Name=Replicase polyprotein 1ab;
CC         IsoId=P0DTD1-1; Sequence=External;
CC   -!- DOMAIN: The hydrophobic domains (HD) could mediate the membrane
CC       association of the replication complex and thereby alter the
CC       architecture of the host cell membrane. {ECO:0000250|UniProtKB:P0C6U8}.
CC   -!- PTM: Specific enzymatic cleavages in vivo by its own proteases yield
CC       mature proteins. 3CL-PRO and PL-PRO proteinases are autocatalytically
CC       processed. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- POLYMORPHISM: Variant B.1.1.7 is also called Variant Of Concern (VOC)
CC       202012/01, Variant Under Investigation (VUI) 202012/01, or 20B/501Y.V1.
CC       {ECO:0000305|PubMed:33413740}.
CC   -!- POLYMORPHISM: Variant Omicron/BA.1 and BA.2 belong to a lineage first
CC       isolated in South Africa (November 2021). {ECO:0000305}.
CC   -!- POLYMORPHISM: Variant Omicron/BQ.1.1 belongs to a lineage first
CC       isolated in Nigeria (November 2022). {ECO:0000305}.
CC   -!- POLYMORPHISM: Variant Omicron/XBB.1.5 belongs to a lineage first
CC       isolated in United States (November 2022). It is the result of
CC       recombination between omicron BJ.1 and BM.1.1. Moreover XBB.1.5 do not
CC       express ORF8. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Replicase polyprotein 1a]: Produced by conventional
CC       translation. {ECO:0000250|UniProtKB:P0C6U8}.
CC   -!- SIMILARITY: Belongs to the coronaviruses polyprotein 1ab family.
CC       {ECO:0000305}.
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DR   EMBL; MN908947; QHD43415.1; ALT_FRAME; Genomic_RNA.
DR   PDB; 6Y2E; X-ray; 1.75 A; A=3264-3569.
DR   PDB; 6Y2F; X-ray; 2.16 A; A=3264-3569.
DR   PDB; 6Y2G; X-ray; 2.16 A; A=3264-3569.
DR   PDB; 6YHU; X-ray; 2.00 A; A/C=3860-3930, B/D=4018-4134.
DR   PDB; 6YYT; EM; 2.90 A; B=3948-4133, C=3860-3932.
DR   PDB; 7BV2; EM; 2.50 A; C=3860-3942, B=3943-4140.
DR   PDB; 7C33; X-ray; 3.83 A; A/B/C/D=1025-1195.
DR   PDB; 7CZ4; X-ray; 2.64 A; A/B=1025-1195.
DR   PDB; 7D3I; X-ray; 2.00 A; A=3264-3569.
DR   PDB; 7D47; X-ray; 1.97 A; A/B=1564-1880.
DR   PDB; 7D64; X-ray; 2.45 A; A=3264-3569.
DR   PDB; 7D6H; X-ray; 1.60 A; A=1563-1878.
DR   PDB; 7DAT; X-ray; 2.75 A; A=3264-3569.
DR   PDB; 7DAU; X-ray; 1.72 A; A=3264-3569.
DR   PDB; 7DAV; X-ray; 1.77 A; A=3264-3569.
DR   PDB; 7DCD; X-ray; 2.57 A; A/C/E/G=3860-3942, B/D/F/H=4019-4140.
DR   PDB; 7DGB; X-ray; 1.68 A; A=3264-3569.
DR   PDB; 7DGF; X-ray; 1.64 A; A=3264-3569.
DR   PDB; 7DGG; X-ray; 2.00 A; A/B=3264-3569.
DR   PDB; 7DGH; X-ray; 1.97 A; A=3264-3569.
DR   PDB; 7DGI; X-ray; 1.90 A; A/B=3264-3569.
DR   PDB; 7DHJ; X-ray; 1.96 A; A=3264-3569.
DR   PDB; 7DJR; X-ray; 1.45 A; A=3264-3569.
DR   PDB; 7DK1; X-ray; 1.90 A; A/B=3264-3569.
DR   PDB; 7DPP; X-ray; 2.10 A; A=3264-3564.
DR   PDB; 7DPU; X-ray; 1.75 A; A/B=3264-3569.
DR   PDB; 7DPV; X-ray; 2.35 A; A/B/C/D=3264-3569.
DR   PDB; 7E35; X-ray; 2.40 A; A/B=1564-1878.
DR   PDB; 7EIN; X-ray; 1.70 A; A/B=3264-3569.
DR   PDB; 7EIZ; EM; -; C=3860-3942.
DR   PDB; 7EN8; X-ray; 1.83 A; A/B=3264-3569.
DR   PDB; 7EN9; X-ray; 1.90 A; A=3264-3569.
DR   PDB; 7EXM; X-ray; 1.96 A; A/B/C/D=181-456.
DR   PDB; 7FAY; X-ray; 2.10 A; A=3264-3569.
DR   PDB; 7FAZ; X-ray; 2.10 A; A/B=3264-3569.
DR   PDB; 7JIR; X-ray; 2.09 A; A=1564-1878.
DR   PDB; 7JIT; X-ray; 1.95 A; A=1564-1878.
DR   PDB; 7JIV; X-ray; 2.05 A; A=1564-1878.
DR   PDB; 7JIW; X-ray; 2.30 A; A=1564-1878.
DR   PDB; 7JN2; X-ray; 1.93 A; A=1564-1878.
DR   PDB; 7JRN; X-ray; 2.48 A; A/J=1564-1878.
DR   PDB; 7KOJ; X-ray; 2.02 A; A=1564-1878.
DR   PDB; 7KOK; X-ray; 2.00 A; A=1564-1878.
DR   PDB; 7KOL; X-ray; 2.58 A; A=1564-1878.
DR   PDB; 7KRX; X-ray; 2.72 A; A=1564-1878.
DR   PDB; 7M1Y; X-ray; 2.02 A; A/B=1564-1878.
DR   PDB; 7NT1; X-ray; 2.85 A; A/B=3264-3569.
DR   PDB; 7NT2; X-ray; 2.15 A; A/B=3264-3569.
DR   PDB; 7NT3; X-ray; 2.33 A; A/B=3264-3569.
DR   PDB; 7NTQ; X-ray; 1.50 A; A=3264-3569.
DR   PDB; 7NTT; X-ray; 1.74 A; A/B=3264-3569.
DR   PDB; 7NTV; X-ray; 2.06 A; A/B=3264-3569.
DR   PDB; 7NTW; X-ray; 1.81 A; A=3264-3569.
DR   PDB; 7NUK; X-ray; 2.19 A; A/B=3264-3569.
DR   PDB; 7NW2; X-ray; 2.10 A; A/B=3264-3569.
DR   PDB; 7NWX; X-ray; 1.80 A; A=3264-3569.
DR   PDB; 7NXH; X-ray; 2.10 A; A=3264-3569.
DR   PDB; 7OFS; X-ray; 1.90 A; A=1564-1878.
DR   PDB; 7OFT; X-ray; 1.95 A; A=1564-1878.
DR   PDB; 7OFU; X-ray; 1.72 A; AAA=1564-1878.
DR   PDB; 7P51; X-ray; 1.47 A; A=3264-3569.
DR   PDB; 7QCG; X-ray; 1.75 A; A=1564-1878.
DR   PDB; 7QCH; X-ray; 1.88 A; A=1564-1878.
DR   PDB; 7QCI; X-ray; 1.76 A; A=1564-1878.
DR   PDB; 7QCJ; X-ray; 1.84 A; A=1564-1878.
DR   PDB; 7QCK; X-ray; 1.92 A; A=1564-1878.
DR   PDB; 7QCM; X-ray; 1.77 A; A=1564-1878.
DR   PDB; 7QL8; X-ray; 1.81 A; AAA=3264-3564.
DR   PDB; 7RBR; X-ray; 1.88 A; A=1564-1878.
DR   PDB; 7RBS; X-ray; 2.98 A; A/C/E/G/I=1564-1878.
DR   PDB; 7RZC; X-ray; 2.04 A; A/B/C=1564-1878.
DR   PDB; 7SDR; X-ray; 2.72 A; A/B/C=1564-1878.
DR   PDB; 7SGU; X-ray; 1.79 A; A=1564-1878.
DR   PDB; 7SGV; X-ray; 2.00 A; A=1564-1878.
DR   PDB; 7SGW; X-ray; 1.95 A; A=1564-1878.
DR   PDB; 7SQE; X-ray; 2.00 A; A/B/C=1564-1878.
DR   PDB; 7TIA; X-ray; 1.64 A; A=3264-3569.
DR   PDB; 7TIU; X-ray; 1.65 A; A=3264-3569.
DR   PDB; 7TIV; X-ray; 2.08 A; A=3264-3569.
DR   PDB; 7TIW; X-ray; 1.68 A; A=3264-3569.
DR   PDB; 7TIX; X-ray; 2.00 A; A=3264-3569.
DR   PDB; 7TIY; X-ray; 1.79 A; A=3264-3569.
DR   PDB; 7TIZ; X-ray; 1.55 A; A=3264-3569.
DR   PDB; 7TJ0; X-ray; 2.17 A; A=3264-3569.
DR   PDB; 7TLL; X-ray; 1.63 A; A/B=3264-3569.
DR   PDB; 7TOB; X-ray; 2.05 A; A=3264-3569.
DR   PDB; 7TUU; X-ray; 1.85 A; A=3264-3569.
DR   PDB; 7TVS; X-ray; 1.89 A; A=3264-3569.
DR   PDB; 7TVX; X-ray; 2.09 A; A=3264-3569.
DR   PDB; 7TZJ; X-ray; 2.66 A; A/B=1564-1878.
DR   PDB; 7U28; X-ray; 1.68 A; A/B=3264-3569.
DR   PDB; 7U29; X-ray; 2.09 A; A/B=3264-3569.
DR   PDB; 7UJ9; X-ray; 2.25 A; A/C=3264-3462.
DR   PDB; 7UJG; X-ray; 1.80 A; A/B=3268-3458.
DR   PDB; 7UJU; X-ray; 1.85 A; A/B=3264-3459.
DR   PDB; 7UV5; X-ray; 1.45 A; A=1564-1878.
DR   PDB; 7V1T; X-ray; 2.56 A; A=3264-3569.
DR   PDB; 7V7M; X-ray; 2.08 A; A=3264-3569.
DR   PDB; 7VFA; X-ray; 1.75 A; E=3264-3569.
DR   PDB; 7VFB; X-ray; 2.00 A; A=3264-3569.
DR   PDB; 7VH8; X-ray; 1.59 A; A=3264-3569.
DR   PDB; 7VIC; X-ray; 2.10 A; A=3264-3569.
DR   PDB; 7VJW; X-ray; 2.20 A; A/B=3264-3569.
DR   PDB; 7VJX; X-ray; 2.20 A; A/B=3264-3569.
DR   PDB; 7VJY; X-ray; 1.90 A; A=3264-3569.
DR   PDB; 7VJZ; X-ray; 1.90 A; A=3264-3569.
DR   PDB; 7VK0; X-ray; 2.10 A; A/B=3264-3569.
DR   PDB; 7VK1; X-ray; 1.93 A; A=3264-3569.
DR   PDB; 7VK2; X-ray; 2.00 A; A=3264-3569.
DR   PDB; 7VK3; X-ray; 2.10 A; A/B=3264-3569.
DR   PDB; 7VK4; X-ray; 2.10 A; A/B=3264-3569.
DR   PDB; 7VK5; X-ray; 2.17 A; A/B=3264-3569.
DR   PDB; 7VK6; X-ray; 2.25 A; A/B=3264-3569.
DR   PDB; 7VK7; X-ray; 2.40 A; A/B=3264-3569.
DR   PDB; 7VK8; X-ray; 2.40 A; A=3264-3569.
DR   PDB; 7VLP; X-ray; 1.50 A; A/B=3265-3569.
DR   PDB; 7VLQ; X-ray; 1.94 A; A/B=3266-3565.
DR   PDB; 7VTH; X-ray; 2.00 A; A/B=3263-3569.
DR   PDB; 7VU6; X-ray; 1.80 A; A/B=3264-3569.
DR   PDB; 7VVT; X-ray; 2.51 A; A/B=3264-3569.
DR   PDB; 7W9G; X-ray; 2.50 A; A=3264-3569.
DR   PDB; 7WO1; X-ray; 2.15 A; A=3264-3569.
DR   PDB; 7WO2; X-ray; 1.96 A; A=3264-3569.
DR   PDB; 7WO3; X-ray; 2.01 A; A=3264-3569.
DR   PDB; 7WOF; X-ray; 1.72 A; A=3264-3569.
DR   PDB; 7WQB; X-ray; 1.87 A; A=3264-3569.
DR   PDB; 7WYM; X-ray; 2.05 A; A=3264-3569.
DR   PDB; 7WYP; X-ray; 2.30 A; A/B=3264-3569.
DR   PDB; 7WZO; X-ray; 2.64 A; B/C=819-929.
DR   PDB; 7X6J; X-ray; 1.50 A; A=3264-3569.
DR   PDB; 7X6K; X-ray; 2.34 A; A=3264-3569.
DR   PDB; 7XAR; X-ray; 1.60 A; A/B=3264-3569.
DR   PDB; 7XB3; X-ray; 2.08 A; A/B=3264-3569.
DR   PDB; 7XB4; X-ray; 2.07 A; A/B=3264-3569.
DR   PDB; 7XC3; X-ray; 1.70 A; A/B=1369-1491.
DR   PDB; 7XC4; X-ray; 2.10 A; A/B=1369-1493.
DR   PDB; 7XQ6; X-ray; 2.00 A; A=3264-3569.
DR   PDB; 7XQ7; X-ray; 2.35 A; A=3264-3569.
DR   PDB; 7XRS; X-ray; 1.93 A; A/B=3266-3564.
DR   PDB; 7YBG; X-ray; 1.90 A; A=1564-1877.
DR   PDB; 7Z0P; X-ray; 2.52 A; AAA=3264-3567.
DR   PDB; 7Z4S; X-ray; 1.70 A; A/B=3264-3569.
DR   PDB; 8AYS; X-ray; 1.37 A; B=10-126.
DR   PDB; 8AZC; X-ray; 0.93 A; A=1024-1197.
DR   PDB; 8AZD; X-ray; 2.00 A; A/B=1024-1197.
DR   PDB; 8B0S; X-ray; 2.42 A; A=3264-3564.
DR   PDB; 8B0T; X-ray; 2.40 A; A=3264-3564.
DR   PDB; 8C9L; X-ray; 1.70 A; AAA=3264-3565.
DR   PDB; 8C9O; X-ray; 1.69 A; AAA/BBB=3264-3569.
DR   PDB; 8CRF; X-ray; 1.15 A; A=10-126.
DR   PDB; 8CRM; X-ray; 1.42 A; A=10-126.
DR   PDB; 8CX9; X-ray; 3.50 A; A/B/C/D=1564-1878.
DR   PDB; 8DI3; X-ray; 1.50 A; A=3264-3569.
DR   PDB; 8DKJ; X-ray; 2.11 A; A=3264-3569.
DR   PDB; 8EIR; EM; 2.49 A; C/D=3860-4392.
DR   PDB; 8FIG; X-ray; 1.75 A; A=3264-3569.
DR   PDB; 8G62; X-ray; 2.17 A; A/B/C=1564-1878.
DR   PDB; 8GQC; X-ray; 1.35 A; A=1231-1494.
DR   PDB; 8GQT; X-ray; 2.09 A; D=3264-3566.
DR   PDB; 8GTV; X-ray; 1.80 A; A/B=3264-3569.
DR   PDB; 8GTW; X-ray; 1.85 A; A/B=3264-3569.
DR   PDB; 8GVD; X-ray; 2.00 A; A=3264-3569.
DR   PDB; 8GVY; X-ray; 2.50 A; A=3264-3569.
DR   PDB; 8GW1; EM; 3.31 A; C=3860-3942.
DR   PDB; 8GWB; EM; 2.75 A; C=3860-3942.
DR   PDB; 8GWE; EM; 2.66 A; C=3860-3942.
DR   PDB; 8GWF; EM; 3.39 A; C=3860-3942.
DR   PDB; 8GWG; EM; 3.37 A; C=3860-3942.
DR   PDB; 8GWI; EM; 3.18 A; C=3860-3942.
DR   PDB; 8GWN; EM; 3.38 A; C=3860-3942.
DR   PDB; 8GWO; EM; 3.80 A; C=3860-3942.
DR   PDB; 8GXG; X-ray; 1.69 A; A=3264-3569.
DR   PDB; 8GXH; X-ray; 1.59 A; A=3264-3569.
DR   PDB; 8GXI; X-ray; 1.69 A; A=3264-3569.
DR   PDB; 8GY6; EM; -; C=3860-3942.
DR   PDB; 8GZB; X-ray; 2.70 A; A=3264-3569.
DR   PDB; 8H3G; X-ray; 1.46 A; A/B=3264-3569.
DR   PDB; 8H3K; X-ray; 1.80 A; A/B=3264-3569.
DR   PDB; 8H3L; X-ray; 2.30 A; A/B/C/D=3264-3569.
DR   PDB; 8H4Y; X-ray; 2.25 A; A=3264-3569.
DR   PDB; 8H51; X-ray; 2.18 A; A=3264-3569.
DR   PDB; 8H57; X-ray; 1.55 A; A=3264-3569.
DR   PDB; 8H5F; X-ray; 1.79 A; A=3264-3569.
DR   PDB; 8H5P; X-ray; 1.67 A; A=3264-3569.
DR   PDB; 8H6I; X-ray; 1.90 A; A=3264-3569.
DR   PDB; 8H6N; X-ray; 1.65 A; A=3264-3569.
DR   PDB; 8H7K; X-ray; 1.45 A; A=3264-3569.
DR   PDB; 8H7W; X-ray; 1.60 A; A=3264-3568.
DR   PDB; 8H82; X-ray; 1.93 A; A=3264-3569.
DR   PDB; 8HBK; X-ray; 1.80 A; A=3264-3569.
DR   PDB; 8HBL; X-ray; 1.58 A; A=1235-1494.
DR   PDB; 8HHT; X-ray; 1.95 A; A=3264-3569.
DR   PDB; 8HHU; X-ray; 2.26 A; A=3264-3569.
DR   PDB; 8HI9; X-ray; 2.28 A; A/B=3264-3569.
DR   PDB; 8HOL; X-ray; 1.82 A; A=3264-3569.
DR   PDB; 8HOM; X-ray; 1.56 A; A=3264-3569.
DR   PDB; 8HOZ; X-ray; 2.83 A; A=3264-3569.
DR   PDB; 8HQG; X-ray; 1.88 A; A/B=3266-3564.
DR   PDB; 8HQH; X-ray; 1.58 A; A/B=3266-3564.
DR   PDB; 8HQI; X-ray; 1.55 A; A/B=3265-3563.
DR   PDB; 8HQJ; X-ray; 1.74 A; A/B=3266-3564.
DR   PDB; 8HTV; X-ray; 2.04 A; A=3264-3569.
DR   PDB; 8HUR; X-ray; 1.64 A; A/B=3266-3563.
DR   PDB; 8HUV; X-ray; 1.97 A; A/B=3266-3564.
DR   PDB; 8HUW; X-ray; 1.75 A; A/B=3266-3564.
DR   PDB; 8HUX; X-ray; 1.74 A; A/B=3266-3564.
DR   PDB; 8HVK; X-ray; 1.63 A; A/B=3266-3563.
DR   PDB; 8HVL; X-ray; 1.45 A; A/B=3266-3564.
DR   PDB; 8HVM; X-ray; 1.48 A; A/B=3266-3566.
DR   PDB; 8HVN; X-ray; 1.90 A; A/B=3266-3563.
DR   PDB; 8HVO; X-ray; 1.65 A; A/B=3266-3564.
DR   PDB; 8HVU; X-ray; 2.29 A; A/B=3266-3564.
DR   PDB; 8HVV; X-ray; 1.95 A; A/B=3266-3564.
DR   PDB; 8HVW; X-ray; 2.05 A; A/B=3266-3564.
DR   PDB; 8HVX; X-ray; 1.75 A; A/B=3266-3564.
DR   PDB; 8HVY; X-ray; 1.97 A; A/B=3266-3564.
DR   PDB; 8HVZ; X-ray; 1.70 A; A/B=3266-3564.
DR   PDB; 8HZR; X-ray; 1.92 A; A/B=3266-3561.
DR   PDB; 8I30; X-ray; 2.00 A; A=3264-3569.
DR   PDB; 8IFP; X-ray; 1.78 A; A=3264-3569.
DR   PDB; 8IFQ; X-ray; 1.96 A; A=3264-3569.
DR   PDB; 8IFR; X-ray; 1.66 A; A=3264-3569.
DR   PDB; 8IFS; X-ray; 2.46 A; A/B=3264-3569.
DR   PDB; 8IFT; X-ray; 1.80 A; A=3264-3569.
DR   PDB; 8IGN; X-ray; 2.02 A; A/B=3264-3569.
DR   PDB; 8IGO; X-ray; 2.00 A; A=3264-3569.
DR   PDB; 8IGX; X-ray; 1.90 A; A=3264-3569.
DR   PDB; 8IGY; X-ray; 1.96 A; A=3264-3569.
DR   PDB; 8IHO; X-ray; 2.55 A; A/C=1564-1878.
DR   PDB; 8ILC; X-ray; 2.20 A; A=2485-2763.
DR   PDB; 8JOP; X-ray; 2.70 A; A=3264-3569.
DR   PDB; 8R0V; X-ray; 2.48 A; A/B/C/D=3264-3569.
DR   PDB; 8R11; X-ray; 1.31 A; A/B=3264-3569.
DR   PDB; 8R12; X-ray; 1.59 A; A/B=3264-3569.
DR   PDB; 8R14; X-ray; 1.34 A; A/B=3264-3569.
DR   PDB; 8R16; X-ray; 1.30 A; A/B=3264-3569.
DR   PDB; 8R19; X-ray; 1.91 A; A=3264-3569.
DR   PDB; 8RV4; X-ray; 2.35 A; B=4254-4392.
DR   PDB; 8RV5; X-ray; 2.05 A; B=4254-4392.
DR   PDB; 8RV6; X-ray; 2.25 A; B=4254-4392.
DR   PDB; 8RV7; X-ray; 1.90 A; B=4254-4392.
DR   PDB; 8RV8; X-ray; 1.70 A; B=4254-4392.
DR   PDB; 8RV9; X-ray; 1.90 A; B=4254-4392.
DR   PDB; 8RVA; X-ray; 1.80 A; B=4254-4392.
DR   PDB; 8RVB; X-ray; 1.95 A; B=4254-4392.
DR   PDB; 8RZC; X-ray; 2.35 A; B=4254-4392.
DR   PDB; 8RZD; X-ray; 2.10 A; B=4254-4392.
DR   PDB; 8RZE; X-ray; 2.00 A; B=4254-4392.
DR   PDB; 8SPJ; X-ray; 2.08 A; A=3264-3569.
DR   PDB; 8SXO; X-ray; 2.76 A; A=3264-3569.
DR   PDB; 8UFM; X-ray; 1.65 A; A=1231-1496.
DR   PDB; 8UIA; X-ray; 1.75 A; A/B=3264-3569.
DR   PDBsum; 6Y2E; -.
DR   PDBsum; 6Y2F; -.
DR   PDBsum; 6Y2G; -.
DR   PDBsum; 6YHU; -.
DR   PDBsum; 6YYT; -.
DR   PDBsum; 7BV2; -.
DR   PDBsum; 7C33; -.
DR   PDBsum; 7CZ4; -.
DR   PDBsum; 7D3I; -.
DR   PDBsum; 7D47; -.
DR   PDBsum; 7D64; -.
DR   PDBsum; 7D6H; -.
DR   PDBsum; 7DAT; -.
DR   PDBsum; 7DAU; -.
DR   PDBsum; 7DAV; -.
DR   PDBsum; 7DCD; -.
DR   PDBsum; 7DGB; -.
DR   PDBsum; 7DGF; -.
DR   PDBsum; 7DGG; -.
DR   PDBsum; 7DGH; -.
DR   PDBsum; 7DGI; -.
DR   PDBsum; 7DHJ; -.
DR   PDBsum; 7DJR; -.
DR   PDBsum; 7DK1; -.
DR   PDBsum; 7DPP; -.
DR   PDBsum; 7DPU; -.
DR   PDBsum; 7DPV; -.
DR   PDBsum; 7E35; -.
DR   PDBsum; 7EIN; -.
DR   PDBsum; 7EIZ; -.
DR   PDBsum; 7EN8; -.
DR   PDBsum; 7EN9; -.
DR   PDBsum; 7EXM; -.
DR   PDBsum; 7FAY; -.
DR   PDBsum; 7FAZ; -.
DR   PDBsum; 7JIR; -.
DR   PDBsum; 7JIT; -.
DR   PDBsum; 7JIV; -.
DR   PDBsum; 7JIW; -.
DR   PDBsum; 7JN2; -.
DR   PDBsum; 7JRN; -.
DR   PDBsum; 7KOJ; -.
DR   PDBsum; 7KOK; -.
DR   PDBsum; 7KOL; -.
DR   PDBsum; 7KRX; -.
DR   PDBsum; 7M1Y; -.
DR   PDBsum; 7NT1; -.
DR   PDBsum; 7NT2; -.
DR   PDBsum; 7NT3; -.
DR   PDBsum; 7NTQ; -.
DR   PDBsum; 7NTT; -.
DR   PDBsum; 7NTV; -.
DR   PDBsum; 7NTW; -.
DR   PDBsum; 7NUK; -.
DR   PDBsum; 7NW2; -.
DR   PDBsum; 7NWX; -.
DR   PDBsum; 7NXH; -.
DR   PDBsum; 7OFS; -.
DR   PDBsum; 7OFT; -.
DR   PDBsum; 7OFU; -.
DR   PDBsum; 7P51; -.
DR   PDBsum; 7QCG; -.
DR   PDBsum; 7QCH; -.
DR   PDBsum; 7QCI; -.
DR   PDBsum; 7QCJ; -.
DR   PDBsum; 7QCK; -.
DR   PDBsum; 7QCM; -.
DR   PDBsum; 7QL8; -.
DR   PDBsum; 7RBR; -.
DR   PDBsum; 7RBS; -.
DR   PDBsum; 7RZC; -.
DR   PDBsum; 7SDR; -.
DR   PDBsum; 7SGU; -.
DR   PDBsum; 7SGV; -.
DR   PDBsum; 7SGW; -.
DR   PDBsum; 7SQE; -.
DR   PDBsum; 7TIA; -.
DR   PDBsum; 7TIU; -.
DR   PDBsum; 7TIV; -.
DR   PDBsum; 7TIW; -.
DR   PDBsum; 7TIX; -.
DR   PDBsum; 7TIY; -.
DR   PDBsum; 7TIZ; -.
DR   PDBsum; 7TJ0; -.
DR   PDBsum; 7TLL; -.
DR   PDBsum; 7TOB; -.
DR   PDBsum; 7TUU; -.
DR   PDBsum; 7TVS; -.
DR   PDBsum; 7TVX; -.
DR   PDBsum; 7TZJ; -.
DR   PDBsum; 7U28; -.
DR   PDBsum; 7U29; -.
DR   PDBsum; 7UJ9; -.
DR   PDBsum; 7UJG; -.
DR   PDBsum; 7UJU; -.
DR   PDBsum; 7UV5; -.
DR   PDBsum; 7V1T; -.
DR   PDBsum; 7V7M; -.
DR   PDBsum; 7VFA; -.
DR   PDBsum; 7VFB; -.
DR   PDBsum; 7VH8; -.
DR   PDBsum; 7VIC; -.
DR   PDBsum; 7VJW; -.
DR   PDBsum; 7VJX; -.
DR   PDBsum; 7VJY; -.
DR   PDBsum; 7VJZ; -.
DR   PDBsum; 7VK0; -.
DR   PDBsum; 7VK1; -.
DR   PDBsum; 7VK2; -.
DR   PDBsum; 7VK3; -.
DR   PDBsum; 7VK4; -.
DR   PDBsum; 7VK5; -.
DR   PDBsum; 7VK6; -.
DR   PDBsum; 7VK7; -.
DR   PDBsum; 7VK8; -.
DR   PDBsum; 7VLP; -.
DR   PDBsum; 7VLQ; -.
DR   PDBsum; 7VTH; -.
DR   PDBsum; 7VU6; -.
DR   PDBsum; 7VVT; -.
DR   PDBsum; 7W9G; -.
DR   PDBsum; 7WO1; -.
DR   PDBsum; 7WO2; -.
DR   PDBsum; 7WO3; -.
DR   PDBsum; 7WOF; -.
DR   PDBsum; 7WQB; -.
DR   PDBsum; 7WYM; -.
DR   PDBsum; 7WYP; -.
DR   PDBsum; 7WZO; -.
DR   PDBsum; 7X6J; -.
DR   PDBsum; 7X6K; -.
DR   PDBsum; 7XAR; -.
DR   PDBsum; 7XB3; -.
DR   PDBsum; 7XB4; -.
DR   PDBsum; 7XC3; -.
DR   PDBsum; 7XC4; -.
DR   PDBsum; 7XQ6; -.
DR   PDBsum; 7XQ7; -.
DR   PDBsum; 7XRS; -.
DR   PDBsum; 7YBG; -.
DR   PDBsum; 7Z0P; -.
DR   PDBsum; 7Z4S; -.
DR   PDBsum; 8AYS; -.
DR   PDBsum; 8AZC; -.
DR   PDBsum; 8AZD; -.
DR   PDBsum; 8B0S; -.
DR   PDBsum; 8B0T; -.
DR   PDBsum; 8C9L; -.
DR   PDBsum; 8C9O; -.
DR   PDBsum; 8CRF; -.
DR   PDBsum; 8CRM; -.
DR   PDBsum; 8CX9; -.
DR   PDBsum; 8DI3; -.
DR   PDBsum; 8DKJ; -.
DR   PDBsum; 8EIR; -.
DR   PDBsum; 8FIG; -.
DR   PDBsum; 8G62; -.
DR   PDBsum; 8GQC; -.
DR   PDBsum; 8GQT; -.
DR   PDBsum; 8GTV; -.
DR   PDBsum; 8GTW; -.
DR   PDBsum; 8GVD; -.
DR   PDBsum; 8GVY; -.
DR   PDBsum; 8GW1; -.
DR   PDBsum; 8GWB; -.
DR   PDBsum; 8GWE; -.
DR   PDBsum; 8GWF; -.
DR   PDBsum; 8GWG; -.
DR   PDBsum; 8GWI; -.
DR   PDBsum; 8GWN; -.
DR   PDBsum; 8GWO; -.
DR   PDBsum; 8GXG; -.
DR   PDBsum; 8GXH; -.
DR   PDBsum; 8GXI; -.
DR   PDBsum; 8GY6; -.
DR   PDBsum; 8GZB; -.
DR   PDBsum; 8H3G; -.
DR   PDBsum; 8H3K; -.
DR   PDBsum; 8H3L; -.
DR   PDBsum; 8H4Y; -.
DR   PDBsum; 8H51; -.
DR   PDBsum; 8H57; -.
DR   PDBsum; 8H5F; -.
DR   PDBsum; 8H5P; -.
DR   PDBsum; 8H6I; -.
DR   PDBsum; 8H6N; -.
DR   PDBsum; 8H7K; -.
DR   PDBsum; 8H7W; -.
DR   PDBsum; 8H82; -.
DR   PDBsum; 8HBK; -.
DR   PDBsum; 8HBL; -.
DR   PDBsum; 8HHT; -.
DR   PDBsum; 8HHU; -.
DR   PDBsum; 8HI9; -.
DR   PDBsum; 8HOL; -.
DR   PDBsum; 8HOM; -.
DR   PDBsum; 8HOZ; -.
DR   PDBsum; 8HQG; -.
DR   PDBsum; 8HQH; -.
DR   PDBsum; 8HQI; -.
DR   PDBsum; 8HQJ; -.
DR   PDBsum; 8HTV; -.
DR   PDBsum; 8HUR; -.
DR   PDBsum; 8HUV; -.
DR   PDBsum; 8HUW; -.
DR   PDBsum; 8HUX; -.
DR   PDBsum; 8HVK; -.
DR   PDBsum; 8HVL; -.
DR   PDBsum; 8HVM; -.
DR   PDBsum; 8HVN; -.
DR   PDBsum; 8HVO; -.
DR   PDBsum; 8HVU; -.
DR   PDBsum; 8HVV; -.
DR   PDBsum; 8HVW; -.
DR   PDBsum; 8HVX; -.
DR   PDBsum; 8HVY; -.
DR   PDBsum; 8HVZ; -.
DR   PDBsum; 8HZR; -.
DR   PDBsum; 8I30; -.
DR   PDBsum; 8IFP; -.
DR   PDBsum; 8IFQ; -.
DR   PDBsum; 8IFR; -.
DR   PDBsum; 8IFS; -.
DR   PDBsum; 8IFT; -.
DR   PDBsum; 8IGN; -.
DR   PDBsum; 8IGO; -.
DR   PDBsum; 8IGX; -.
DR   PDBsum; 8IGY; -.
DR   PDBsum; 8IHO; -.
DR   PDBsum; 8ILC; -.
DR   PDBsum; 8JOP; -.
DR   PDBsum; 8R0V; -.
DR   PDBsum; 8R11; -.
DR   PDBsum; 8R12; -.
DR   PDBsum; 8R14; -.
DR   PDBsum; 8R16; -.
DR   PDBsum; 8R19; -.
DR   PDBsum; 8RV4; -.
DR   PDBsum; 8RV5; -.
DR   PDBsum; 8RV6; -.
DR   PDBsum; 8RV7; -.
DR   PDBsum; 8RV8; -.
DR   PDBsum; 8RV9; -.
DR   PDBsum; 8RVA; -.
DR   PDBsum; 8RVB; -.
DR   PDBsum; 8RZC; -.
DR   PDBsum; 8RZD; -.
DR   PDBsum; 8RZE; -.
DR   PDBsum; 8SPJ; -.
DR   PDBsum; 8SXO; -.
DR   PDBsum; 8UFM; -.
DR   PDBsum; 8UIA; -.
DR   EMDB; EMD-11007; -.
DR   EMDB; EMD-30210; -.
DR   EMDB; EMD-31146; -.
DR   EMDB; EMD-34302; -.
DR   EMDB; EMD-34308; -.
DR   EMDB; EMD-34310; -.
DR   EMDB; EMD-34317; -.
DR   EMDB; EMD-34370; -.
DR   SASBDB; P0DTC1; -.
DR   SMR; P0DTC1; -.
DR   BioGRID; 4383866; 156.
DR   IntAct; P0DTC1; 47.
DR   BindingDB; P0DTC1; -.
DR   DrugBank; DB15797; GC-373.
DR   DrugBank; DB15796; GC-376 free acid.
DR   DNASU; 43740578; -.
DR   Reactome; R-HSA-9694271; Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC).
DR   Reactome; R-HSA-9694301; Maturation of replicase proteins.
DR   Reactome; R-HSA-9694676; Translation of Replicase and Assembly of the Replication Transcription Complex.
DR   Reactome; R-HSA-9694686; Replication of the SARS-CoV-2 genome.
DR   Reactome; R-HSA-9694786; Transcription of SARS-CoV-2 sgRNAs.
DR   Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR   Reactome; R-HSA-9754678; SARS-CoV-2 modulates host translation machinery.
DR   SABIO-RK; P0DTC1; -.
DR   Proteomes; UP000464024; Genome.
DR   GO; GO:0062243; C:double membrane vesicle viral factory outer membrane; TAS:Reactome.
DR   GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0044174; C:host cell endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0044177; C:host cell Golgi apparatus; IEA:UniProtKB-SubCell.
DR   GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:Reactome.
DR   GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0002151; F:G-quadruplex RNA binding; IEA:InterPro.
DR   GO; GO:0019785; F:ISG15-specific peptidase activity; TAS:Reactome.
DR   GO; GO:0008289; F:lipid binding; EXP:DisProt.
DR   GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR   GO; GO:0008242; F:omega peptidase activity; IEA:InterPro.
DR   GO; GO:0003727; F:single-stranded RNA binding; IEA:InterPro.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0039595; P:symbiont-mediated degradation of host mRNA; IEA:UniProtKB-KW.
DR   GO; GO:0039648; P:symbiont-mediated perturbation of host protein ubiquitination; IEA:UniProtKB-KW.
DR   GO; GO:0039548; P:symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity; IEA:UniProtKB-KW.
DR   GO; GO:0039579; P:symbiont-mediated suppression of host ISG15-protein conjugation; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:symbiont-mediated suppression of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0019079; P:viral genome replication; IEA:InterPro.
DR   GO; GO:0019082; P:viral protein processing; IEA:InterPro.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-KW.
DR   CDD; cd21901; alpha_betaCoV_Nsp10; 1.
DR   CDD; cd21560; betaCoV-Nsp6; 1.
DR   CDD; cd21516; betaCoV_Nsp2_SARS-like; 1.
DR   CDD; cd21666; betaCoV_Nsp5_Mpro; 1.
DR   CDD; cd21827; betaCoV_Nsp7; 1.
DR   CDD; cd21831; betaCoV_Nsp8; 1.
DR   CDD; cd21898; betaCoV_Nsp9; 1.
DR   CDD; cd21732; betaCoV_PLPro; 1.
DR   CDD; cd21473; cv_Nsp4_TM; 1.
DR   CDD; cd21563; Macro_cv_SUD-M_Nsp3-like; 1.
DR   CDD; cd21557; Macro_X_Nsp3-like; 1.
DR   CDD; cd22662; SARS-CoV-like_Nsp1_C; 1.
DR   CDD; cd21796; SARS-CoV-like_Nsp1_N; 1.
DR   CDD; cd21822; SARS-CoV-like_Nsp3_NAB; 1.
DR   CDD; cd21525; SUD_C_SARS-CoV_Nsp3; 1.
DR   CDD; cd21717; TM_Y_SARS-CoV-like_Nsp3_C; 1.
DR   CDD; cd21467; Ubl1_cv_Nsp3_N-like; 1.
DR   Gene3D; 1.10.8.1190; -; 1.
DR   Gene3D; 2.60.120.1680; -; 1.
DR   Gene3D; 3.10.20.350; -; 1.
DR   Gene3D; 3.10.20.540; -; 1.
DR   Gene3D; 6.10.140.2090; -; 1.
DR   Gene3D; 1.10.150.420; Coronavirus nonstructural protein 4 C-terminus; 1.
DR   Gene3D; 3.40.30.150; Coronavirus polyprotein cleavage domain; 1.
DR   Gene3D; 3.40.220.10; Leucine Aminopeptidase, subunit E, domain 1; 1.
DR   Gene3D; 1.10.1840.10; main proteinase (3clpro) structure, domain 3; 1.
DR   Gene3D; 3.40.220.20; Nsp3, SUD-M subdomain; 1.
DR   Gene3D; 3.40.220.30; Nsp3, SUD-N subdomain; 1.
DR   Gene3D; 1.10.8.370; nsp7 replicase; 1.
DR   Gene3D; 3.30.70.3540; Nsp8 replicase, head domain; 1.
DR   Gene3D; 2.40.10.250; Replicase NSP9; 1.
DR   Gene3D; 3.40.50.11020; Replicase polyprotein, nucleic acid-binding domain; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR   InterPro; IPR046443; a/bCoV_NSP1_glob.
DR   InterPro; IPR046442; bCoV_NSP1_C.
DR   InterPro; IPR043613; CoV_NSP2_C.
DR   InterPro; IPR047573; CoV_NSP2_M.
DR   InterPro; IPR049894; COV_NSP3_3ECTO.
DR   InterPro; IPR043611; CoV_NSP3_C.
DR   InterPro; IPR047566; CoV_NSP3_Y.
DR   InterPro; IPR032505; CoV_NSP4_C.
DR   InterPro; IPR043612; CoV_NSP4_N.
DR   InterPro; IPR022733; DPUP_SUD_C_bCoV.
DR   InterPro; IPR002589; Macro_dom.
DR   InterPro; IPR043472; Macro_dom-like.
DR   InterPro; IPR044371; Macro_X_NSP3-like.
DR   InterPro; IPR036333; NSP10_sf_CoV.
DR   InterPro; IPR021590; NSP1_glob_bCoV.
DR   InterPro; IPR038030; NSP1_glob_sf_bCoV.
DR   InterPro; IPR043615; NSP2_N_CoV.
DR   InterPro; IPR044389; NSP2_SARS-CoV-like.
DR   InterPro; IPR024375; NSP3_bCoV.
DR   InterPro; IPR047567; NSP3_G2M_bCoV.
DR   InterPro; IPR024358; NSP3_N_bCoV.
DR   InterPro; IPR032592; NSP3_NAB_bCoV.
DR   InterPro; IPR042570; NSP3_NAB_bCoV_sf.
DR   InterPro; IPR038166; NSP3_PL2pro_sf_bCoV.
DR   InterPro; IPR038400; NSP3_SUD-M_sf_bCoV.
DR   InterPro; IPR044864; NSP3_SUD-N_bCoV.
DR   InterPro; IPR043478; NSP3_SUD-N_sf_bCoV.
DR   InterPro; IPR044357; NSP3_Ubl1_dom_CoV.
DR   InterPro; IPR044353; Nsp3_Ubl2_dom_CoV.
DR   InterPro; IPR038083; NSP3A-like.
DR   InterPro; IPR038123; NSP4_C_sf_CoV.
DR   InterPro; IPR044367; NSP6_betaCoV.
DR   InterPro; IPR043610; NSP6_CoV.
DR   InterPro; IPR014828; NSP7_CoV.
DR   InterPro; IPR037204; NSP7_sf_CoV.
DR   InterPro; IPR014829; NSP8_CoV.
DR   InterPro; IPR037230; NSP8_sf_CoV.
DR   InterPro; IPR014822; NSP9_CoV.
DR   InterPro; IPR036499; NSP9_sf_CoV.
DR   InterPro; IPR013016; Peptidase_C16_CoV.
DR   InterPro; IPR008740; Peptidase_C30_CoV.
DR   InterPro; IPR043477; Peptidase_C30_dom3_CoV.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR043177; PLpro_N_sf_CoV.
DR   InterPro; IPR043503; PLpro_palm_finger_dom_CoV.
DR   InterPro; IPR043178; PLpro_thumb_sf_CoV.
DR   InterPro; IPR018995; RNA_synth_NSP10_CoV.
DR   PANTHER; PTHR11106; GANGLIOSIDE INDUCED DIFFERENTIATION ASSOCIATED PROTEIN 2-RELATED; 1.
DR   PANTHER; PTHR11106:SF111; MACRO DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF16251; bCoV_NAB; 1.
DR   Pfam; PF11501; bCoV_NSP1; 1.
DR   Pfam; PF12379; bCoV_NSP3_N; 1.
DR   Pfam; PF12124; bCoV_SUD_C; 1.
DR   Pfam; PF11633; bCoV_SUD_M; 1.
DR   Pfam; PF09401; CoV_NSP10; 1.
DR   Pfam; PF19212; CoV_NSP2_C; 1.
DR   Pfam; PF19211; CoV_NSP2_N; 1.
DR   Pfam; PF19218; CoV_NSP3_C; 1.
DR   Pfam; PF16348; CoV_NSP4_C; 1.
DR   Pfam; PF19217; CoV_NSP4_N; 1.
DR   Pfam; PF19213; CoV_NSP6; 1.
DR   Pfam; PF08716; CoV_NSP7; 1.
DR   Pfam; PF08717; CoV_NSP8; 1.
DR   Pfam; PF08710; CoV_NSP9; 1.
DR   Pfam; PF08715; CoV_peptidase; 1.
DR   Pfam; PF01661; Macro; 1.
DR   Pfam; PF05409; Peptidase_C30; 1.
DR   SMART; SM00506; A1pp; 1.
DR   SUPFAM; SSF144246; Coronavirus NSP10-like; 1.
DR   SUPFAM; SSF140367; Coronavirus NSP7-like; 1.
DR   SUPFAM; SSF143076; Coronavirus NSP8-like; 1.
DR   SUPFAM; SSF52949; Macro domain-like; 1.
DR   SUPFAM; SSF159936; NSP3A-like; 1.
DR   SUPFAM; SSF101816; Replicase NSP9; 1.
DR   SUPFAM; SSF160099; SARS Nsp1-like; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS51963; BCOV_NSP1_C; 1.
DR   PROSITE; PS51942; BCOV_NSP3C_C; 1.
DR   PROSITE; PS51941; BCOV_NSP3C_M; 1.
DR   PROSITE; PS51994; BCOV_NSP3E_G2M; 1.
DR   PROSITE; PS51945; BCOV_NSP3E_NAB; 1.
DR   PROSITE; PS51993; COV_3ECTO; 1.
DR   PROSITE; PS51952; COV_EXON_MTASE_COACT; 1.
DR   PROSITE; PS51962; COV_NSP1; 1.
DR   PROSITE; PS51991; COV_NSP2_C; 1.
DR   PROSITE; PS51990; COV_NSP2_M; 1.
DR   PROSITE; PS51989; COV_NSP2_N; 1.
DR   PROSITE; PS51992; COV_NSP3_Y; 1.
DR   PROSITE; PS51943; COV_NSP3A_UBL; 1.
DR   PROSITE; PS51944; COV_NSP3D_UBL; 1.
DR   PROSITE; PS51946; COV_NSP4C; 1.
DR   PROSITE; PS51949; COV_NSP7; 1.
DR   PROSITE; PS51950; COV_NSP8; 1.
DR   PROSITE; PS51951; COV_NSP9_SSRNA_BD; 1.
DR   PROSITE; PS00867; CPSASE_2; 1.
DR   PROSITE; PS51442; M_PRO; 1.
DR   PROSITE; PS51154; MACRO; 1.
DR   PROSITE; PS51124; PEPTIDASE_C16; 1.
DR   PROSITE; PS51940; SARS_NSP3C_N; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Activation of host autophagy by virus;
KW   Decay of host mRNAs by virus; Disulfide bond; Endonuclease;
KW   Eukaryotic host gene expression shutoff by virus;
KW   Eukaryotic host translation shutoff by virus; Host cytoplasm;
KW   Host endoplasmic reticulum; Host endosome;
KW   Host gene expression shutoff by virus; Host Golgi apparatus; Host membrane;
KW   Host mRNA suppression by virus; 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 IRF3 by virus; Inhibition of host ISG15 by virus;
KW   Inhibition of host RLR pathway by virus;
KW   Interferon antiviral system evasion; Membrane; Metal-binding;
KW   Methyltransferase;
KW   Modulation of host ubiquitin pathway by viral deubiquitinase;
KW   Modulation of host ubiquitin pathway by virus; Nuclease; Protease;
KW   Reference proteome; Repeat; Ribosomal frameshifting; RNA-binding;
KW   Thiol protease; Transferase; Transmembrane; Transmembrane helix;
KW   Ubl conjugation pathway; Viral immunoevasion; Zinc; Zinc-finger.
FT   CHAIN           1..4405
FT                   /note="Replicase polyprotein 1a"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6U8"
FT                   /id="PRO_0000449634"
FT   CHAIN           1..180
FT                   /note="Host translation inhibitor nsp1"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449635"
FT   CHAIN           181..818
FT                   /note="Non-structural protein 2"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449636"
FT   CHAIN           819..2763
FT                   /note="Papain-like protease nsp3"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449637"
FT   CHAIN           2764..3263
FT                   /note="Non-structural protein 4"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449638"
FT   CHAIN           3264..3569
FT                   /note="3C-like proteinase nsp5"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449639"
FT   CHAIN           3570..3859
FT                   /note="Non-structural protein 6"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449640"
FT   CHAIN           3860..3942
FT                   /note="Non-structural protein 7"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449641"
FT   CHAIN           3943..4140
FT                   /note="Non-structural protein 8"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449642"
FT   CHAIN           4141..4253
FT                   /note="RNA-capping enzyme subunit nsp9"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449643"
FT   CHAIN           4254..4392
FT                   /note="Non-structural protein 10"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449644"
FT   CHAIN           4393..4405
FT                   /note="Non-structural protein 11"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449645"
FT   TOPO_DOM        1..2225
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        2226..2246
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2247..2317
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        2318..2338
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2339..2775
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        2776..2796
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2797..3044
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        3045..3065
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3066..3099
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        3100..3120
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3121..3127
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        3128..3148
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3149..3586
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305|PubMed:35551511"
FT   TRANSMEM        3587..3607
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3608
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305|PubMed:35551511"
FT   TRANSMEM        3609..3629
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3630..3634
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305|PubMed:35551511"
FT   TRANSMEM        3635..3655
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3656..3673
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305|PubMed:35551511"
FT   TRANSMEM        3674..3694
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3695..3729
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305|PubMed:35551511"
FT   TRANSMEM        3730..3750
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3751..3778
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305|PubMed:35551511"
FT   TRANSMEM        3779..3799
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3800..4405
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305|PubMed:35551511"
FT   DOMAIN          12..127
FT                   /note="CoV Nsp1 globular"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01307"
FT   DOMAIN          148..179
FT                   /note="BetaCoV Nsp1 C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01308"
FT   DOMAIN          183..456
FT                   /note="CoV Nsp2 N-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   DOMAIN          458..688
FT                   /note="CoV Nsp2 middle"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01334"
FT   DOMAIN          690..818
FT                   /note="CoV Nsp2 C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01335"
FT   DOMAIN          821..929
FT                   /note="Ubiquitin-like 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT   DOMAIN          1025..1194
FT                   /note="Macro 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT   DOMAIN          1231..1359
FT                   /note="Macro 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT   DOMAIN          1367..1494
FT                   /note="Macro 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT   DOMAIN          1496..1561
FT                   /note="DPUP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01289"
FT   DOMAIN          1565..1620
FT                   /note="Ubiquitin-like 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT   DOMAIN          1634..1898
FT                   /note="Peptidase C16"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   DOMAIN          1911..2021
FT                   /note="Nucleic acid-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01290"
FT   DOMAIN          2046..2155
FT                   /note="G2M"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01338"
FT   DOMAIN          2247..2317
FT                   /note="3Ecto"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01337"
FT   DOMAIN          2395..2763
FT                   /note="CoV Nsp3 Y"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   DOMAIN          3165..3263
FT                   /note="Nsp4C"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01291"
FT   DOMAIN          3264..3569
FT                   /note="Peptidase C30"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT   DOMAIN          3860..3942
FT                   /note="RdRp Nsp7 cofactor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01294"
FT   DOMAIN          3943..4140
FT                   /note="RdRp Nsp8 cofactor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01295"
FT   DOMAIN          4141..4253
FT                   /note="Nsp9 ssRNA-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01296"
FT   DOMAIN          4254..4392
FT                   /note="ExoN/MTase coactivator"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   ZN_FING         1752..1789
FT                   /note="C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   REGION          154..180
FT                   /note="Binding to 40s ribosome mRNA entry channel"
FT                   /evidence="ECO:0000269|PubMed:32680882"
FT   REGION          200..236
FT                   /note="C2H2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   REGION          323..344
FT                   /note="C4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   REGION          370..416
FT                   /note="C2HC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   REGION          926..999
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2395..2485
FT                   /note="Y1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2399..2412
FT                   /note="ZF1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2445..2455
FT                   /note="ZF2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2486..2763
FT                   /note="CoV-Y"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2486..2580
FT                   /note="Y2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2581..2662
FT                   /note="Y3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2663..2763
FT                   /note="Y4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   COMPBIAS        927..947
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        984..999
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1674
FT                   /note="For PL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444,
FT                   ECO:0000269|PubMed:32726803"
FT   ACT_SITE        1835
FT                   /note="For PL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        1849
FT                   /note="For PL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        3304
FT                   /note="For 3CL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772,
FT                   ECO:0000269|PubMed:32198291"
FT   ACT_SITE        3408
FT                   /note="For 3CL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772,
FT                   ECO:0000269|PubMed:32198291"
FT   BINDING         200
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         231
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         234
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         236
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         323
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         326
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         341
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         344
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         370
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         373
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         382
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         416
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         1752
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1755
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1787
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1789
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         2399
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2404
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2409
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2412
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2445
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2448
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2452
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2455
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         4327
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4330
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4336
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4343
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4370
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4373
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4381
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4383
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   SITE            180..181
FT                   /note="Cleavage; by PL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            818..819
FT                   /note="Cleavage; by PL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            2763..2764
FT                   /note="Cleavage; by PL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            3263..3264
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            3569..3570
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            3859..3860
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            3942..3943
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            4140..4141
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            4253..4254
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            4392..4393
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   DISULFID        2263..2291
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01337"
FT   DISULFID        2282..2288
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01337"
FT   VARIANT         47
FT                   /note="K -> R (in strain: Omicron/XBB.1.5, Omicron/EG.5.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         135
FT                   /note="S -> R (in strain: Omicron/BA.2, Omicron/BA.2.12.1,
FT                   Omicron/BA.2.75, Omicron/BA.4, Omicron/BA.5, Omicron/
FT                   BQ.1.1, Omicron/XBB.1.5, Omicron/EG.5.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         141..143
FT                   /note="Missing (in strain: Omicron/BA.4)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         265
FT                   /note="T -> I (in strain: Iota/B.1.526, Beta/B.1.351 and
FT                   Epsilon/B.1.427/B.1.429)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         556
FT                   /note="Q -> K (in strain: Omicron/BQ.1.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         690
FT                   /note="A -> V (in strain: Omicron/EG.5.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         842
FT                   /note="T -> I (in strain: Omicron/BA.2, Omicron/BA.2.12.1,
FT                   Omicron/BA.2.75, Omicron/BA.4, Omicron/BA.5, Omicron/
FT                   BQ.1.1, Omicron/XBB.1.5, Omicron/EG.5.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         856
FT                   /note="K -> R (in strain: Omicron/BA.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         1001
FT                   /note="T -> I (in strain: Alpha/B.1.1.7)"
FT                   /evidence="ECO:0000305|PubMed:33413740"
FT   VARIANT         1055
FT                   /note="T -> A (in strain: Mu/B.1.621)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         1188
FT                   /note="S -> L (in strain: Gamma/P.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         1221
FT                   /note="S -> L (in strain: Omicron/BA.2.75)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         1246
FT                   /note="T -> I (in strain: Lambda/C.37)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         1307
FT                   /note="G -> S (in strain: Omicron/BA.2, Omicron/BA.2.12.1,
FT                   Omicron/BA.2.75, Omicron/BA.4, Omicron/BA.5, Omicron/
FT                   BQ.1.1, Omicron/XBB.1.5, Omicron/EG.5.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         1538
FT                   /note="T -> I (in strain: Mu/B.1.621)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         1554
FT                   /note="D -> G (in strain: Theta/P.3)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         1567
FT                   /note="T -> I (in strain: Kappa/B.1.617.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         1640
FT                   /note="P -> S (in strain: Omicron/BA.2.75)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         1655
FT                   /note="K -> N (in strain: Beta/B.1.351)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         1708
FT                   /note="A -> D (in strain: Alpha/B.1.1.7)"
FT                   /evidence="ECO:0000305|PubMed:33413740"
FT   VARIANT         1795
FT                   /note="K -> Q (in strain: Gamma/P.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         1819
FT                   /note="G -> S (in strain: Omicron/EG.5.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         2007
FT                   /note="T -> I (in strain: Eta/B.1.525)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         2083..2084
FT                   /note="SL -> I (in strain: Omicron/BA.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         2230
FT                   /note="I -> T (in strain: Alpha/B.1.1.7)"
FT                   /evidence="ECO:0000305|PubMed:33413740"
FT   VARIANT         2287
FT                   /note="P -> S (in strain: Lambda/C.37)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         2387
FT                   /note="F -> V (in strain: Lambda/C.37)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         2625
FT                   /note="S -> F (in strain: Theta/P.3)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         2710
FT                   /note="A -> T (in strain: Omicron/BA.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         2980
FT                   /note="D -> N (in strain: Theta/P.3)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3027
FT                   /note="L -> F (in strain: Omicron/BA.2, Omicron/BA.2.12.1,
FT                   Omicron/BA.2.75, Omicron/BA.4, Omicron/BA.5, Omicron/
FT                   BQ.1.1, Omicron/XBB.1.5, Omicron/EG.5.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3090
FT                   /note="T -> I (in strain: Omicron/BA.2, Omicron/BA.2.12.1,
FT                   Omicron/BA.2.75, Omicron/BA.4, Omicron/BA.5, Omicron/
FT                   BQ.1.1, Omicron/XBB.1.5, Omicron/EG.5.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3143
FT                   /note="A -> V (in strain: Omicron/EG.5.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3201
FT                   /note="L -> F (in strain: Omicron/BA.2, Omicron/BA.2.12.1,
FT                   Omicron/BA.2.75, Omicron/XBB.1.5, Omicron/EG.5.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3201
FT                   /note="L -> P (in strain: Iota/B.1.526, Lambda/C.37 and
FT                   Theta/P.3)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3255
FT                   /note="T -> I (in strain: Lambda/C.37, Mu/B.1.621, Omicron/
FT                   BA.1, Omicron/BA.2, Omicron/BA.2.12.1, Omicron/BA.2.75,
FT                   Omicron/BA.4, Omicron/BA.5, Omicron/BQ.1.1, Omicron/
FT                   XBB.1.5, Omicron/EG.5.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3353
FT                   /note="K -> R (in strain: Beta/B.1.351)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3395
FT                   /note="P -> H (in strain: Omicron/BA.1, Omicron/BA.2,
FT                   Omicron/BA.2.12.1, Omicron/BA.2.75, Omicron/BA.4, Omicron/
FT                   BA.5, Omicron/BQ.1.1, Omicron/XBB.1.5, Omicron/EG.5.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3468
FT                   /note="L -> V (in strain: Zeta/P.2)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3646
FT                   /note="T -> A (in strain: Kappa/B.1.617.1)"
FT   VARIANT         3674..3676
FT                   /note="Missing (in strain: Omicron/BA.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3675..3677
FT                   /note="Missing (in strain: Omicron/BA.2, Omicron/BA.2.12.1,
FT                   Omicron/BA.2.75, Omicron/BA.4, Omicron/BA.5, Omicron/
FT                   BQ.1.1, Omicron/XBB.1.5, Omicron/EG.5.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3675
FT                   /note="S -> K (in strain: Alpha/B.1.1.7, Beta/B.1.351,
FT                   Gamma/P.1, Eta/B.1.525, Iota/B.1.526 and Lambda/C.37)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3676..3678
FT                   /note="Missing (in strain: Alpha/B.1.1.7, Beta/B.1.351,
FT                   Gamma/P.1, Eta/B.1.525, Iota/B.1.526 and Lambda/C.37)"
FT                   /evidence="ECO:0000305, ECO:0000305|PubMed:33413740"
FT   VARIANT         3681
FT                   /note="D -> E (in strain: Theta/P.3)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3729
FT                   /note="Q -> R (in strain: Mu/B.1.621)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3758
FT                   /note="I -> V (in strain: Omicron/BA.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3829
FT                   /note="L -> F (in strain: Omicron/BQ.1.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         3930
FT                   /note="L -> F (in strain: Theta/P.3 and Zeta/P.2)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         4060
FT                   /note="N -> S (in strain: Omicron/BA.2.75)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         4175
FT                   /note="T -> I (in strain: Omicron/EG.5.1)"
FT                   /evidence="ECO:0000305"
FT   MUTAGEN         154..157
FT                   /note="YEDF->AEDA: Complete loss of ribosome binding and
FT                   cellular translation inhibition."
FT                   /evidence="ECO:0000269|PubMed:32908316"
FT   MUTAGEN         164..165
FT                   /note="KH->AA: Complete loss of ribosome binding and
FT                   cellular translation inhibition."
FT                   /evidence="ECO:0000269|PubMed:32908316"
FT   MUTAGEN         164
FT                   /note="K->A: Complete loss of ribosome binding and cellular
FT                   translation inhibition."
FT                   /evidence="ECO:0000269|PubMed:32680882"
FT   MUTAGEN         165
FT                   /note="H->A: Complete loss of ribosome binding and cellular
FT                   translation inhibition."
FT                   /evidence="ECO:0000269|PubMed:32680882"
FT   MUTAGEN         171..175
FT                   /note="RELMR->EELME: Complete loss of ribosome binding and
FT                   cellular translation inhibition."
FT                   /evidence="ECO:0000269|PubMed:32908316"
FT   MUTAGEN         442
FT                   /note="G->V: Significant loss of GIGYF2-mediated mRNA
FT                   repression."
FT                   /evidence="ECO:0000269|PubMed:35878012"
FT   MUTAGEN         1629
FT                   /note="V->A: Partial loss of ISG15 cleavage in vitro."
FT                   /evidence="ECO:0000269|PubMed:32726803"
FT   MUTAGEN         1632
FT                   /note="F->A: Partial loss of ISG15 cleavage in vitro."
FT                   /evidence="ECO:0000269|PubMed:32726803"
FT   MUTAGEN         1638
FT                   /note="T->A: Partial loss of ubiquitin cleavage in vitro;
FT                   no effect on ISG15 cleavage in vitro."
FT                   /evidence="ECO:0000269|PubMed:32726803"
FT   MUTAGEN         1638
FT                   /note="T->L: Increased cleavage of ubiquitin in vitro; no
FT                   effect on ISG15 cleavage in vitro."
FT                   /evidence="ECO:0000269|PubMed:32726803"
FT   MUTAGEN         1674
FT                   /note="C->A: Unable to remove host IFIH1 (MDA5)
FT                   ISGylation."
FT                   /evidence="ECO:0000269|PubMed:33727702"
FT   MUTAGEN         1674
FT                   /note="C->S: Complete loss of PL-pro activity."
FT                   /evidence="ECO:0000269|PubMed:32726803"
FT   MUTAGEN         1831
FT                   /note="Y->G,T: Reduced inhibition by GRL-0617."
FT                   /evidence="ECO:0000269|PubMed:32726803"
FT   MUTAGEN         3408
FT                   /note="C->A: Complete loss of 3C-like proteinase nsp5
FT                   cleavage."
FT                   /evidence="ECO:0000269|PubMed:35594856"
FT   MUTAGEN         3675..3677
FT                   /note="Missing: Faster formation of double membrane
FT                   vesicles."
FT                   /evidence="ECO:0000269|PubMed:35551511"
FT   MUTAGEN         3789
FT                   /note="F->Q: Complete loss of ER zippering."
FT                   /evidence="ECO:0000269|PubMed:35551511"
FT   MUTAGEN         3791
FT                   /note="T->W: Complete loss of ER zippering."
FT                   /evidence="ECO:0000269|PubMed:35551511"
FT   MUTAGEN         4141
FT                   /note="N->A,D: Complete loss of RNA guanylyltransferase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:35944563"
FT   MUTAGEN         4142
FT                   /note="N->A: Complete loss of RNA guanylyltransferase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:35944563"
FT   STRAND          1235..1238
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   HELIX           1243..1246
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   TURN            1247..1249
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   STRAND          1253..1257
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   HELIX           1265..1268
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   HELIX           1277..1281
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   STRAND          1290..1293
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   STRAND          1296..1300
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   HELIX           1310..1317
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   STRAND          1322..1327
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   HELIX           1333..1335
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   HELIX           1339..1347
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   STRAND          1349..1355
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   HELIX           1375..1385
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   STRAND          1388..1392
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   HELIX           1396..1405
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   STRAND          1413..1425
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   HELIX           1431..1441
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   STRAND          1445..1447
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   TURN            1453..1455
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   HELIX           1459..1466
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   STRAND          1473..1476
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   HELIX           1480..1488
FT                   /evidence="ECO:0007829|PDB:8UFM"
FT   STRAND          1567..1578
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   STRAND          1580..1585
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   HELIX           1590..1594
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   STRAND          1595..1599
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   HELIX           1611..1613
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   STRAND          1617..1620
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   HELIX           1625..1635
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   HELIX           1642..1653
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   TURN            1671..1673
FT                   /evidence="ECO:0007829|PDB:7TZJ"
FT   HELIX           1674..1683
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   STRAND          1690..1692
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   HELIX           1693..1704
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   HELIX           1708..1717
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   HELIX           1728..1737
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   STRAND          1745..1752
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   TURN            1753..1755
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   STRAND          1756..1763
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   HELIX           1765..1768
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   STRAND          1769..1772
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   HELIX           1776..1781
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   STRAND          1783..1786
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   STRAND          1790..1816
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   STRAND          1822..1830
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   STRAND          1833..1849
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   STRAND          1852..1869
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   STRAND          1871..1874
FT                   /evidence="ECO:0007829|PDB:7D6H"
FT   HELIX           3274..3277
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3280..3285
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3288..3295
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3298..3302
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   HELIX           3303..3306
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   HELIX           3310..3313
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   HELIX           3317..3322
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   HELIX           3326..3328
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3330..3333
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3336..3338
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3340..3346
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3349..3356
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3363..3366
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3374..3381
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3384..3392
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3411..3416
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3419..3429
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   TURN            3431..3433
FT                   /evidence="ECO:0007829|PDB:8H57"
FT   STRAND          3435..3438
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3444..3447
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3450..3453
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   HELIX           3464..3476
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   HELIX           3490..3499
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   HELIX           3507..3512
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   HELIX           3514..3520
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   HELIX           3524..3537
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   STRAND          3544..3546
FT                   /evidence="ECO:0007829|PDB:7XB4"
FT   STRAND          3547..3549
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   HELIX           3556..3562
FT                   /evidence="ECO:0007829|PDB:8H7K"
FT   HELIX           3862..3878
FT                   /evidence="ECO:0007829|PDB:8GWB"
FT   HELIX           3881..3883
FT                   /evidence="ECO:0007829|PDB:8GWB"
FT   HELIX           3885..3898
FT                   /evidence="ECO:0007829|PDB:8GWB"
FT   HELIX           3906..3919
FT                   /evidence="ECO:0007829|PDB:8GWB"
FT   STRAND          3922..3924
FT                   /evidence="ECO:0007829|PDB:8GWB"
FT   TURN            3927..3929
FT                   /evidence="ECO:0007829|PDB:8GWB"
SQ   SEQUENCE   4405 AA;  489989 MW;  7F8A21148A7A7E2A CRC64;
     MESLVPGFNE KTHVQLSLPV LQVRDVLVRG FGDSVEEVLS EARQHLKDGT CGLVEVEKGV
     LPQLEQPYVF IKRSDARTAP HGHVMVELVA ELEGIQYGRS GETLGVLVPH VGEIPVAYRK
     VLLRKNGNKG AGGHSYGADL KSFDLGDELG TDPYEDFQEN WNTKHSSGVT RELMRELNGG
     AYTRYVDNNF CGPDGYPLEC IKDLLARAGK ASCTLSEQLD FIDTKRGVYC CREHEHEIAW
     YTERSEKSYE LQTPFEIKLA KKFDTFNGEC PNFVFPLNSI IKTIQPRVEK KKLDGFMGRI
     RSVYPVASPN ECNQMCLSTL MKCDHCGETS WQTGDFVKAT CEFCGTENLT KEGATTCGYL
     PQNAVVKIYC PACHNSEVGP EHSLAEYHNE SGLKTILRKG GRTIAFGGCV FSYVGCHNKC
     AYWVPRASAN IGCNHTGVVG EGSEGLNDNL LEILQKEKVN INIVGDFKLN EEIAIILASF
     SASTSAFVET VKGLDYKAFK QIVESCGNFK VTKGKAKKGA WNIGEQKSIL SPLYAFASEA
     ARVVRSIFSR TLETAQNSVR VLQKAAITIL DGISQYSLRL IDAMMFTSDL ATNNLVVMAY
     ITGGVVQLTS QWLTNIFGTV YEKLKPVLDW LEEKFKEGVE FLRDGWEIVK FISTCACEIV
     GGQIVTCAKE IKESVQTFFK LVNKFLALCA DSIIIGGAKL KALNLGETFV THSKGLYRKC
     VKSREETGLL MPLKAPKEII FLEGETLPTE VLTEEVVLKT GDLQPLEQPT SEAVEAPLVG
     TPVCINGLML LEIKDTEKYC ALAPNMMVTN NTFTLKGGAP TKVTFGDDTV IEVQGYKSVN
     ITFELDERID KVLNEKCSAY TVELGTEVNE FACVVADAVI KTLQPVSELL TPLGIDLDEW
     SMATYYLFDE SGEFKLASHM YCSFYPPDED EEEGDCEEEE FEPSTQYEYG TEDDYQGKPL
     EFGATSAALQ PEEEQEEDWL DDDSQQTVGQ QDGSEDNQTT TIQTIVEVQP QLEMELTPVV
     QTIEVNSFSG YLKLTDNVYI KNADIVEEAK KVKPTVVVNA ANVYLKHGGG VAGALNKATN
     NAMQVESDDY IATNGPLKVG GSCVLSGHNL AKHCLHVVGP NVNKGEDIQL LKSAYENFNQ
     HEVLLAPLLS AGIFGADPIH SLRVCVDTVR TNVYLAVFDK NLYDKLVSSF LEMKSEKQVE
     QKIAEIPKEE VKPFITESKP SVEQRKQDDK KIKACVEEVT TTLEETKFLT ENLLLYIDIN
     GNLHPDSATL VSDIDITFLK KDAPYIVGDV VQEGVLTAVV IPTKKAGGTT EMLAKALRKV
     PTDNYITTYP GQGLNGYTVE EAKTVLKKCK SAFYILPSII SNEKQEILGT VSWNLREMLA
     HAEETRKLMP VCVETKAIVS TIQRKYKGIK IQEGVVDYGA RFYFYTSKTT VASLINTLND
     LNETLVTMPL GYVTHGLNLE EAARYMRSLK VPATVSVSSP DAVTAYNGYL TSSSKTPEEH
     FIETISLAGS YKDWSYSGQS TQLGIEFLKR GDKSVYYTSN PTTFHLDGEV ITFDNLKTLL
     SLREVRTIKV FTTVDNINLH TQVVDMSMTY GQQFGPTYLD GADVTKIKPH NSHEGKTFYV
     LPNDDTLRVE AFEYYHTTDP SFLGRYMSAL NHTKKWKYPQ VNGLTSIKWA DNNCYLATAL
     LTLQQIELKF NPPALQDAYY RARAGEAANF CALILAYCNK TVGELGDVRE TMSYLFQHAN
     LDSCKRVLNV VCKTCGQQQT TLKGVEAVMY MGTLSYEQFK KGVQIPCTCG KQATKYLVQQ
     ESPFVMMSAP PAQYELKHGT FTCASEYTGN YQCGHYKHIT SKETLYCIDG ALLTKSSEYK
     GPITDVFYKE NSYTTTIKPV TYKLDGVVCT EIDPKLDNYY KKDNSYFTEQ PIDLVPNQPY
     PNASFDNFKF VCDNIKFADD LNQLTGYKKP ASRELKVTFF PDLNGDVVAI DYKHYTPSFK
     KGAKLLHKPI VWHVNNATNK ATYKPNTWCI RCLWSTKPVE TSNSFDVLKS EDAQGMDNLA
     CEDLKPVSEE VVENPTIQKD VLECNVKTTE VVGDIILKPA NNSLKITEEV GHTDLMAAYV
     DNSSLTIKKP NELSRVLGLK TLATHGLAAV NSVPWDTIAN YAKPFLNKVV STTTNIVTRC
     LNRVCTNYMP YFFTLLLQLC TFTRSTNSRI KASMPTTIAK NTVKSVGKFC LEASFNYLKS
     PNFSKLINII IWFLLLSVCL GSLIYSTAAL GVLMSNLGMP SYCTGYREGY LNSTNVTIAT
     YCTGSIPCSV CLSGLDSLDT YPSLETIQIT ISSFKWDLTA FGLVAEWFLA YILFTRFFYV
     LGLAAIMQLF FSYFAVHFIS NSWLMWLIIN LVQMAPISAM VRMYIFFASF YYVWKSYVHV
     VDGCNSSTCM MCYKRNRATR VECTTIVNGV RRSFYVYANG GKGFCKLHNW NCVNCDTFCA
     GSTFISDEVA RDLSLQFKRP INPTDQSSYI VDSVTVKNGS IHLYFDKAGQ KTYERHSLSH
     FVNLDNLRAN NTKGSLPINV IVFDGKSKCE ESSAKSASVY YSQLMCQPIL LLDQALVSDV
     GDSAEVAVKM FDAYVNTFSS TFNVPMEKLK TLVATAEAEL AKNVSLDNVL STFISAARQG
     FVDSDVETKD VVECLKLSHQ SDIEVTGDSC NNYMLTYNKV ENMTPRDLGA CIDCSARHIN
     AQVAKSHNIA LIWNVKDFMS LSEQLRKQIR SAAKKNNLPF KLTCATTRQV VNVVTTKIAL
     KGGKIVNNWL KQLIKVTLVF LFVAAIFYLI TPVHVMSKHT DFSSEIIGYK AIDGGVTRDI
     ASTDTCFANK HADFDTWFSQ RGGSYTNDKA CPLIAAVITR EVGFVVPGLP GTILRTTNGD
     FLHFLPRVFS AVGNICYTPS KLIEYTDFAT SACVLAAECT IFKDASGKPV PYCYDTNVLE
     GSVAYESLRP DTRYVLMDGS IIQFPNTYLE GSVRVVTTFD SEYCRHGTCE RSEAGVCVST
     SGRWVLNNDY YRSLPGVFCG VDAVNLLTNM FTPLIQPIGA LDISASIVAG GIVAIVVTCL
     AYYFMRFRRA FGEYSHVVAF NTLLFLMSFT VLCLTPVYSF LPGVYSVIYL YLTFYLTNDV
     SFLAHIQWMV MFTPLVPFWI TIAYIICIST KHFYWFFSNY LKRRVVFNGV SFSTFEEAAL
     CTFLLNKEMY LKLRSDVLLP LTQYNRYLAL YNKYKYFSGA MDTTSYREAA CCHLAKALND
     FSNSGSDVLY QPPQTSITSA VLQSGFRKMA FPSGKVEGCM VQVTCGTTTL NGLWLDDVVY
     CPRHVICTSE DMLNPNYEDL LIRKSNHNFL VQAGNVQLRV IGHSMQNCVL KLKVDTANPK
     TPKYKFVRIQ PGQTFSVLAC YNGSPSGVYQ CAMRPNFTIK GSFLNGSCGS VGFNIDYDCV
     SFCYMHHMEL PTGVHAGTDL EGNFYGPFVD RQTAQAAGTD TTITVNVLAW LYAAVINGDR
     WFLNRFTTTL NDFNLVAMKY NYEPLTQDHV DILGPLSAQT GIAVLDMCAS LKELLQNGMN
     GRTILGSALL EDEFTPFDVV RQCSGVTFQS AVKRTIKGTH HWLLLTILTS LLVLVQSTQW
     SLFFFLYENA FLPFAMGIIA MSAFAMMFVK HKHAFLCLFL LPSLATVAYF NMVYMPASWV
     MRIMTWLDMV DTSLSGFKLK DCVMYASAVV LLILMTARTV YDDGARRVWT LMNVLTLVYK
     VYYGNALDQA ISMWALIISV TSNYSGVVTT VMFLARGIVF MCVEYCPIFF ITGNTLQCIM
     LVYCFLGYFC TCYFGLFCLL NRYFRLTLGV YDYLVSTQEF RYMNSQGLLP PKNSIDAFKL
     NIKLLGVGGK PCIKVATVQS KMSDVKCTSV VLLSVLQQLR VESSSKLWAQ CVQLHNDILL
     AKDTTEAFEK MVSLLSVLLS MQGAVDINKL CEEMLDNRAT LQAIASEFSS LPSYAAFATA
     QEAYEQAVAN GDSEVVLKKL KKSLNVAKSE FDRDAAMQRK LEKMADQAMT QMYKQARSED
     KRAKVTSAMQ TMLFTMLRKL DNDALNNIIN NARDGCVPLN IIPLTTAAKL MVVIPDYNTY
     KNTCDGTTFT YASALWEIQQ VVDADSKIVQ LSEISMDNSP NLAWPLIVTA LRANSAVKLQ
     NNELSPVALR QMSCAAGTTQ TACTDDNALA YYNTTKGGRF VLALLSDLQD LKWARFPKSD
     GTGTIYTELE PPCRFVTDTP KGPKVKYLYF IKGLNNLNRG MVLGSLAATV RLQAGNATEV
     PANSTVLSFC AFAVDAAKAY KDYLASGGQP ITNCVKMLCT HTGTGQAITV TPEANMDQES
     FGGASCCLYC RCHIDHPNPK GFCDLKGKYV QIPTTCANDP VGFTLKNTVC TVCGMWKGYG
     CSCDQLREPM LQSADAQSFL NGFAV
//