R1A_SARS2
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 03-AUG-2022, entry version 12.
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=Non-structural protein 9;
DE Short=nsp9;
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 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 [7]
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 [8]
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 [9]
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 [10]
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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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).
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]: May play a role in the modulation
CC of host cell survival signaling pathway by interacting with host PHB
CC and PHB2. Indeed, these two proteins play a role in maintaining the
CC functional integrity of the mitochondria and protecting cells from
CC various stresses. {ECO:0000250|UniProtKB:P0C6X7}.
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 (By
CC similarity). Antagonizes innate immune induction of type I interferon
CC by blocking the phosphorylation, dimerization and subsequent nuclear
CC translocation of host IRF3 (PubMed:32733001). Prevents also host NF-
CC kappa-B signaling (By similarity). In addition, PL-PRO possesses a
CC deubiquitinating/deISGylating activity and processes both 'Lys-48'- and
CC 'Lys-63'-linked polyubiquitin chains from cellular substrates
CC (PubMed:32726803). Cleaves preferentially ISG15 from antiviral protein
CC IFIH1 (MDA5), but not DDX58 (RIG-I) (PubMed:33727702). Can play a role
CC in host ADP-ribosylation by ADP-ribose (PubMed:32578982).
CC {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:32578982,
CC ECO:0000269|PubMed:32726803, ECO:0000269|PubMed:32733001,
CC ECO:0000269|PubMed:33727702}.
CC -!- FUNCTION: [Non-structural protein 4]: Participates in the assembly of
CC virally-induced cytoplasmic double-membrane vesicles necessary for
CC viral replication. {ECO:0000250|UniProtKB:P0C6X7}.
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). Also able to bind an ADP-ribose-
CC 1''-phosphate (ADRP) (By similarity) (PubMed:32198291,
CC PubMed:32272481). {ECO:0000250|UniProtKB:P0C6X7,
CC ECO:0000269|PubMed:32198291, ECO:0000269|PubMed:32272481,
CC ECO:0000269|PubMed:32321856}.
CC -!- FUNCTION: [Non-structural protein 6]: Plays a role in the initial
CC induction of autophagosomes from host reticulum endoplasmic (By
CC similarity). Later, limits the expansion of these phagosomes that are
CC no longer able to deliver viral components to lysosomes (By
CC similarity). Binds to host TBK1 without affecting TBK1 phosphorylation;
CC the interaction with TBK1 decreases IRF3 phosphorylation, which leads
CC to reduced IFN-beta production (PubMed:32979938).
CC {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:32979938}.
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: [Non-structural protein 9]: May participate in viral
CC replication by acting as a ssRNA-binding protein (By similarity).
CC Interacts with ribosome signal recognition particle RNA (SRP)
CC (PubMed:33080218). Together with NSP9, suppress protein integration
CC into the cell membrane, thereby disrupting host immune defenses
CC (PubMed:33080218). {ECO:0000250|UniProtKB:P0C6X7,
CC ECO:0000269|PubMed:33080218}.
CC -!- FUNCTION: [Non-structural protein 10]: Plays a pivotal role in viral
CC transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16
CC 2'-O-methyltransferase activities. Therefore plays an essential role in
CC viral mRNAs cap methylation. {ECO:0000250|UniProtKB:P0C6X7}.
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:
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 -!- 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: [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]: Interacts with host TBK1; this
CC interaction decreases IRF3 phosphorylation by 57%, which leads to
CC reduced IFN-beta production. {ECO:0000269|PubMed:32979938}.
CC -!- SUBUNIT: [Non-structural protein 7]: Eight copies of nsp7 and eight
CC copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling
CC ring structure (By similarity). Interacts with RNA-directed RNA
CC polymerase (PubMed:32277040, PubMed:32358203, PubMed:32438371,
CC PubMed:32526208). {ECO:0000250|UniProtKB:P0C6X7,
CC ECO:0000269|PubMed:32277040, ECO:0000269|PubMed:32358203,
CC ECO:0000269|PubMed:32438371, ECO:0000269|PubMed:32526208}.
CC -!- SUBUNIT: [Non-structural protein 8]: Eight copies of nsp7 and eight
CC copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling
CC ring structure (By similarity). Interacts with RNA-directed RNA
CC polymerase (PubMed:32277040, PubMed:32358203, PubMed:32438371,
CC PubMed:32526208). {ECO:0000250|UniProtKB:P0C6X7,
CC ECO:0000269|PubMed:32277040, ECO:0000269|PubMed:32358203,
CC ECO:0000269|PubMed:32438371, ECO:0000269|PubMed:32526208}.
CC -!- SUBUNIT: [Non-structural protein 9]: Is a dimer.
CC {ECO:0000250|UniProtKB:P0C6X7}.
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 membrane
CC {ECO:0000250|UniProtKB:P0C6X7}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P0C6X7}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P0C6X7}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4]: Host membrane
CC {ECO:0000250|UniProtKB:P0C6X7}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P0C6X7}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P0C6X7}. Note=Localizes in virally-induced
CC cytoplasmic double-membrane vesicles. {ECO:0000250|UniProtKB:P0C6X7}.
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 membrane
CC {ECO:0000250|UniProtKB:P0C6X7}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P0C6X7}.
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: [Non-structural protein 9]: 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: [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 -!- 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 RefSeq; YP_009725295.1; NC_045512.2.
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; 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; 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; 7TLL; X-ray; 1.63 A; A/B=3264-3569.
DR PDB; 7TOB; X-ray; 2.05 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; 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; 7WO1; X-ray; 2.15 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 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; 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; 7RBR; -.
DR PDBsum; 7RBS; -.
DR PDBsum; 7RZC; -.
DR PDBsum; 7SDR; -.
DR PDBsum; 7SGU; -.
DR PDBsum; 7SGV; -.
DR PDBsum; 7SGW; -.
DR PDBsum; 7SQE; -.
DR PDBsum; 7TLL; -.
DR PDBsum; 7TOB; -.
DR PDBsum; 7TVS; -.
DR PDBsum; 7TVX; -.
DR PDBsum; 7TZJ; -.
DR PDBsum; 7U28; -.
DR PDBsum; 7U29; -.
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; 7WO1; -.
DR PDBsum; 7WO3; -.
DR PDBsum; 7WOF; -.
DR SASBDB; P0DTC1; -.
DR SMR; P0DTC1; -.
DR BioGRID; 4383866; 89.
DR IntAct; P0DTC1; 47.
DR DrugBank; DB15797; GC-373.
DR DrugBank; DB15796; GC-376 free acid.
DR DNASU; 43740578; -.
DR GeneID; 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:0044165; C:host cell endoplasmic reticulum; 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:0016021; C:integral component of 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: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:0016740; F:transferase activity; IEA:InterPro.
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:0039519; P:modulation by virus of host autophagy; ISS:UniProtKB.
DR GO; GO:0039648; P:modulation by virus of host protein ubiquitination; IEA:UniProtKB-KW.
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:0039547; P:suppression by virus of host TRAF activity; 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; cd21560; betaCoV-Nsp6; 1.
DR CDD; cd21666; betaCoV_Nsp5_Mpro; 1.
DR CDD; cd21516; cv_beta_Nsp2_SARS-like; 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; cd21525; SUD_C_SARS-CoV_Nsp3; 1.
DR CDD; cd21467; Ubl1_cv_Nsp3_N-like; 1.
DR CDD; cd21466; Ubl2_cv_PLpro_N_Nsp3-like; 1.
DR Gene3D; 1.10.150.420; -; 1.
DR Gene3D; 1.10.1840.10; -; 1.
DR Gene3D; 1.10.8.1190; -; 1.
DR Gene3D; 1.10.8.370; -; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.40.10.250; -; 1.
DR Gene3D; 2.60.120.1680; -; 1.
DR Gene3D; 3.10.20.350; -; 1.
DR Gene3D; 3.10.20.540; -; 1.
DR Gene3D; 3.30.70.3540; -; 1.
DR Gene3D; 3.40.220.10; -; 1.
DR Gene3D; 3.40.220.20; -; 1.
DR Gene3D; 3.40.220.30; -; 1.
DR Gene3D; 3.40.30.150; -; 1.
DR Gene3D; 3.40.50.11020; -; 1.
DR InterPro; IPR043613; CoV_NSP2_C.
DR InterPro; IPR043611; CoV_NSP3_C.
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_bCoV.
DR InterPro; IPR038030; NSP1_sf_bCoV.
DR InterPro; IPR043615; NSP2_N_CoV.
DR InterPro; IPR044389; NSP2_SARS-CoV-like.
DR InterPro; IPR024375; NSP3_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_NAR; 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; SSF101816; SSF101816; 1.
DR SUPFAM; SSF140367; SSF140367; 1.
DR SUPFAM; SSF143076; SSF143076; 1.
DR SUPFAM; SSF144246; SSF144246; 1.
DR SUPFAM; SSF159936; SSF159936; 1.
DR SUPFAM; SSF160099; SSF160099; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF52949; SSF52949; 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; 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_Y3; 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; 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 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; 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="Non-structural protein 9"
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 TRANSMEM 2226..2246
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2318..2338
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2339..2359
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2361..2381
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2776..2796
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3045..3065
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3077..3097
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3100..3120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3128..3148
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3165..3185
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3587..3607
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3609..3629
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3635..3655
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3674..3694
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3730..3750
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3779..3799
FT /note="Helical"
FT /evidence="ECO:0000255"
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 2660..2763
FT /note="CoV Nsp3 Y3"
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 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 PL1-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444,
FT ECO:0000269|PubMed:32726803"
FT ACT_SITE 1835
FT /note="For PL2-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 4327
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4330
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4336
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4343
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4370
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4373
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4381
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4383
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
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 VARIANT 135
FT /note="S -> R (in strain: Omicron/BA.2, Omicron/BA.2.12.1,
FT Omicron/BA.4, Omicron/BA.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 842
FT /note="T -> I (in strain: Omicron/BA.2, Omicron/BA.2.12.1,
FT Omicron/BA.4, Omicron/BA.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 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.4, Omicron/BA.5)"
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 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.4, Omicron/BA.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.4, Omicron/BA.5)"
FT /evidence="ECO:0000305"
FT VARIANT 3201
FT /note="L -> F (in strain: Omicron/BA.2, Omicron/BA.2.12.1)"
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.4,
FT Omicron/BA.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.4, Omicron/BA.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.4, Omicron/BA.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 3930
FT /note="L -> F (in strain: Theta/P.3 and Zeta/P.2)"
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 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 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:7SGU"
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 TURN 3431..3433
FT /evidence="ECO:0007829|PDB:7VH8"
FT STRAND 3435..3438
FT /evidence="ECO:0007829|PDB:7P51"
FT STRAND 3444..3447
FT /evidence="ECO:0007829|PDB:7VH8"
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 3565..3568
FT /evidence="ECO:0007829|PDB:7DGG"
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
