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 28-JUN-2023, entry version 17. 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. 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. 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 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] 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 [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] 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 [26] 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 [27] 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 [28] 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:33479166, PubMed:33080218, PubMed:32680882, PubMed:32908316). CC The C-terminus binds to and obstructs ribosomal mRNA entry tunnel CC (PubMed:33479166, PubMed:33080218, PubMed:32680882, PubMed:32908316). CC Thereby inhibits antiviral response triggered by innate immunity or CC interferons (PubMed:33080218, PubMed:32680882, PubMed:32979938). 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). Viral mRNAs less susceptible to nsp1-mediated inhibition CC of translation, because of their 5'-end leader sequence CC (PubMed:32908316, 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}. 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:32358203, PubMed:32277040, 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:32358203, PubMed:32277040, 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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; 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; 7Z0P; X-ray; 2.52 A; AAA=3264-3567. DR PDB; 8ASQ; X-ray; 1.15 A; B=10-126. DR PDB; 8AYS; X-ray; 1.37 A; B=10-126. DR PDB; 8AZ9; X-ray; 1.42 A; B=10-126. DR PDB; 8B0S; X-ray; 2.42 A; A=3264-3564. DR PDB; 8B0T; X-ray; 2.40 A; A=3264-3564. DR PDB; 8CX9; X-ray; 3.50 A; A/B/C/D=1564-1878. DR PDB; 8G62; X-ray; 2.17 A; A/B/C=1564-1878. 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; 8HHT; X-ray; 1.95 A; A=3264-3569. DR PDB; 8HHU; X-ray; 2.26 A; A=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; 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; 7Z0P; -. DR PDBsum; 8ASQ; -. DR PDBsum; 8AYS; -. DR PDBsum; 8AZ9; -. DR PDBsum; 8B0S; -. DR PDBsum; 8B0T; -. DR PDBsum; 8CX9; -. DR PDBsum; 8G62; -. DR PDBsum; 8GWB; -. DR PDBsum; 8GWE; -. DR PDBsum; 8GWF; -. DR PDBsum; 8GWG; -. DR PDBsum; 8GWI; -. DR PDBsum; 8GWN; -. DR PDBsum; 8GWO; -. DR PDBsum; 8HHT; -. DR PDBsum; 8HHU; -. DR SASBDB; P0DTC1; -. DR SMR; P0DTC1; -. DR BioGRID; 4383866; 155. 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:0039714; C:cytoplasmic viral factory; ISS:UniProtKB. DR GO; GO:0062243; C:double membrane vesicle viral factory outer membrane; TAS:Reactome. DR GO; GO:0030430; C:host cell cytoplasm; ISS:UniProtKB. 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; ISS:UniProtKB. DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:UniProtKB. DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW. DR GO; GO:0002151; F:G-quadruplex RNA binding; IEA:InterPro. DR GO; GO:0042802; F:identical protein binding; IEA:UniProt. DR GO; GO:0019785; F:ISG15-specific peptidase activity; ISS:UniProtKB. DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW. DR GO; GO:0008242; F:omega peptidase activity; IEA:InterPro. DR GO; GO:0046983; F:protein dimerization activity; ISS:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0003727; F:single-stranded RNA binding; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0039595; P:induction by virus of catabolism of host mRNA; IEA:UniProtKB-KW. 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:0039648; P:modulation by symbiont of host protein ubiquitination; IEA:UniProtKB-KW. DR GO; GO:0039519; P:modulation by virus of host autophagy; ISS:UniProtKB. DR GO; GO:0039690; P:positive stranded viral RNA replication; ISS:UniProtKB. DR GO; GO:0016540; P:protein autoprocessing; ISS:UniProtKB. DR GO; GO:0071108; P:protein K48-linked deubiquitination; ISS:UniProtKB. DR GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW. DR GO; GO:0039579; P:suppression by virus of host ISG15-protein conjugation; ISS:UniProtKB. DR GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; ISS:UniProtKB. DR GO; GO:0039722; P:suppression by virus of host toll-like receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0039527; P:suppression by virus of host TRAF-mediated signal transduction; ISS:UniProtKB. DR GO; GO:0039604; P:suppression by virus of host translation; ISS:UniProtKB. DR GO; GO:0039501; P:suppression by virus of host type I interferon production; ISS:UniProtKB. DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; ISS:UniProtKB. DR GO; GO:0039548; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity; ISS:UniProtKB. DR GO; GO:0019079; P:viral genome replication; IEA:InterPro. DR GO; GO:0019082; P:viral protein processing; IEA:InterPro. DR GO; GO:0039694; P:viral RNA genome replication; ISS:UniProtKB. 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; IPR043611; CoV_NSP3_C. DR InterPro; IPR047566; CoV_NSP3_Y3. 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 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; 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)" 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)" 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 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)" 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)" 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 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)" 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)" 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)" 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)" 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)" 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)" 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 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 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:7P51" FT STRAND 3280..3285 FT /evidence="ECO:0007829|PDB:7P51" FT STRAND 3288..3295 FT /evidence="ECO:0007829|PDB:7P51" FT STRAND 3298..3302 FT /evidence="ECO:0007829|PDB:7P51" FT HELIX 3303..3306 FT /evidence="ECO:0007829|PDB:7P51" FT HELIX 3310..3313 FT /evidence="ECO:0007829|PDB:7P51" FT HELIX 3317..3322 FT /evidence="ECO:0007829|PDB:7P51" FT HELIX 3326..3328 FT /evidence="ECO:0007829|PDB:7P51" FT STRAND 3329..3333 FT /evidence="ECO:0007829|PDB:7P51" FT STRAND 3336..3338 FT /evidence="ECO:0007829|PDB:7P51" FT STRAND 3340..3346 FT /evidence="ECO:0007829|PDB:7P51" FT STRAND 3349..3356 FT /evidence="ECO:0007829|PDB:7P51" FT STRAND 3363..3366 FT /evidence="ECO:0007829|PDB:7P51" FT STRAND 3374..3381 FT /evidence="ECO:0007829|PDB:7P51" FT STRAND 3384..3392 FT /evidence="ECO:0007829|PDB:7P51" FT STRAND 3411..3416 FT /evidence="ECO:0007829|PDB:7P51" FT STRAND 3419..3429 FT /evidence="ECO:0007829|PDB:7P51" FT STRAND 3435..3438 FT /evidence="ECO:0007829|PDB:7P51" FT STRAND 3450..3453 FT /evidence="ECO:0007829|PDB:7P51" FT HELIX 3464..3476 FT /evidence="ECO:0007829|PDB:7P51" FT HELIX 3490..3499 FT /evidence="ECO:0007829|PDB:7P51" FT HELIX 3507..3512 FT /evidence="ECO:0007829|PDB:7P51" FT HELIX 3514..3520 FT /evidence="ECO:0007829|PDB:7P51" FT HELIX 3524..3537 FT /evidence="ECO:0007829|PDB:7P51" FT STRAND 3547..3549 FT /evidence="ECO:0007829|PDB:7P51" FT HELIX 3556..3564 FT /evidence="ECO:0007829|PDB:7P51" FT HELIX 3862..3878 FT /evidence="ECO:0007829|PDB:7EIZ" FT HELIX 3886..3898 FT /evidence="ECO:0007829|PDB:7EIZ" FT HELIX 3904..3920 FT /evidence="ECO:0007829|PDB:7EIZ" FT STRAND 3921..3923 FT /evidence="ECO:0007829|PDB:7EIZ" FT HELIX 3926..3929 FT /evidence="ECO:0007829|PDB:7EIZ" 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 //