ID R1AB_SARS2 Reviewed; 7096 AA. AC P0DTD1; DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot. DT 22-APR-2020, sequence version 1. DT 02-DEC-2020, entry version 5. DE RecName: Full=Replicase polyprotein 1ab; DE Short=pp1ab; DE AltName: Full=ORF1ab 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=Non-structural protein 3; DE Short=nsp3; DE EC=3.4.19.12 {ECO:0000269|PubMed:32726803}; DE EC=3.4.22.-; DE AltName: Full=PL2-PRO; DE AltName: Full=Papain-like protease {ECO:0000303|PubMed:32726803}; 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; DE Short=3CL-PRO; DE Short=3CLp; DE EC=3.4.22.69 {ECO:0000269|PubMed:32198291, ECO:0000269|PubMed:32272481}; 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=RNA-directed RNA polymerase; DE Short=Pol; DE Short=RdRp; DE EC=2.7.7.48; DE AltName: Full=Non-structural protein 12; DE Short=nsp12; DE Contains: DE RecName: Full=Helicase; DE Short=Hel; DE EC=3.6.4.12; DE EC=3.6.4.13; DE AltName: Full=Non-structural protein 13; DE Short=nsp13; DE Contains: DE RecName: Full=Proofreading exoribonuclease; DE Short=ExoN; DE EC=3.1.13.-; DE AltName: Full=Guanine-N7 methyltransferase; DE AltName: Full=Non-structural protein 14; DE Short=nsp14; DE Contains: DE RecName: Full=Uridylate-specific endoribonuclease; DE EC=3.1.-.-; DE AltName: Full=NendoU; DE AltName: Full=Non-structural protein 15; DE Short=nsp15; DE Contains: DE RecName: Full=2'-O-methyltransferase; DE EC=2.1.1.-; DE AltName: Full=Non-structural protein 16; DE Short=nsp16; GN Name=rep; ORFNames=1a-1b; 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 X-RAY CRYSTALLOGRAPHY (2.16 ANGSTROMS) OF 3C-LIKE PROTEINASE AND IN COMPLEX RP 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 [3] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 3C-LIKE PROTEINASE APOENZYME AND RP IN COMPLEX WITH ALPHA-KETOAMIDE 13B INHIBITOR, SUBUNIT (3C-LIKE RP PROTEINASE), FUNCTION (3C-LIKE PROTEINASE), CATALYTIC ACTIVITY (3C-LIKE RP PROTEINASE), ACTIVE SITE (3C-LIKE PROTEINASE), AND ACTIVITY REGULATION RP (3C-LIKE PROTEINASE). 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 0:0-0(2020). RN [4] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 3C-LIKE PROTEINASE APOENZYME AND RP IN COMPLEX WITH MICHAEL ACCEPTOR INHIBITOR N3, FUNCTION (3C-LIKE RP PROTEINASE) (3C-LIKE PROTEINASE), CATALYTIC ACTIVITY (3C-LIKE PROTEINASE), RP AND ACTIVITY REGULATION (3C-LIKE PROTEINASE). 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 0:0-0(2020). RN [5] RP STRUCTURE BY ELECTRON MICROSCOPY (2.9 ANGSTROMS) OF NON-STRUCTURAL PROTEIN RP 7; NON-STRUCTURAL PROTEIN 8 AND RNA-DIRECTED RNA POLYMERASE, SUBUNIT RP (NON-STRUCTURAL PROTEIN 7), SUBUNIT (NON-STRUCTURAL PROTEIN 8), SUBUNIT RP (RNA-DIRECTED RNA POLYMERASE), FUNCTION (NON-STRUCTURAL PROTEIN 7), RP FUNCTION (NON-STRUCTURAL PROTEIN 8), AND FUNCTION (RNA-DIRECTED RNA RP POLYMERASE). 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 0:0-0(2020). RN [6] RP STRUCTURE BY ELECTRON MICROSCOPY (2.5 ANGSTROMS) OF NON-STRUCTURAL PROTEIN RP 7; NON-STRUCTURAL PROTEIN 8 AND RNA-DIRECTED RNA POLYMERASE IN COMPLEX WITH RP REMDESIVIR ANTIVIRAL DRUG AND IN COMPLEX WITH ZINC ION, SUBUNIT RP (NON-STRUCTURAL PROTEIN 7), SUBUNIT (NON-STRUCTURAL PROTEIN 8), SUBUNIT RP (RNA-DIRECTED RNA POLYMERASE), FUNCTION (NON-STRUCTURAL PROTEIN 7), RP FUNCTION (NON-STRUCTURAL PROTEIN 8), FUNCTION (RNA-DIRECTED RNA RP POLYMERASE), CATALYTIC ACTIVITY (RNA-DIRECTED RNA POLYMERASE), AND ACTIVITY RP REGULATION (RNA-DIRECTED RNA POLYMERASE). 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 0:0-0(2020). RN [7] RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 3C-LIKE PROTEINASE APOENZYME IN RP COMPLEX WITH COMPOUND 11A AND COMPOUND 11B, FUNCTION (3C-LIKE PROTEINASE), RP CATALYTIC ACTIVITY (3C-LIKE PROTEINASE), AND ACTIVITY REGULATION (3C-LIKE RP PROTEINASE). 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 0:0-0(2020). RN [8] RP STRUCTURE BY ELECTRON MICROSCOPY (2.9 ANGSTROMS) OF NON-STRUCTURAL PROTEIN RP 7; NON-STRUCTURAL PROTEIN 8 AND RNA-DIRECTED RNA POLYMERASE, SUBUNIT RP (NON-STRUCTURAL PROTEIN 7), SUBUNIT (NON-STRUCTURAL PROTEIN 8), SUBUNIT RP (RNA-DIRECTED RNA POLYMERASE), FUNCTION (NON-STRUCTURAL PROTEIN 7), RP FUNCTION (NON-STRUCTURAL PROTEIN 8), FUNCTION (RNA-DIRECTED RNA RP POLYMERASE), AND CATALYTIC ACTIVITY (RNA-DIRECTED RNA POLYMERASE). 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 0:0-0(2020). RN [9] 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 0:0-0(2020). RN [10] RP STRUCTURE BY ELECTRON MICROSCOPY (2.93 ANGSTROMS) OF NON-STRUCTURAL PROTEIN RP 7; NON-STRUCTURAL PROTEIN 8 AND RNA-DIRECTED RNA POLYMERASE IN COMPLEX WITH RP ZINC ION, SUBUNIT (NON-STRUCTURAL PROTEIN 7), SUBUNIT (NON-STRUCTURAL RP PROTEIN 8), SUBUNIT (RNA-DIRECTED RNA POLYMERASE), FUNCTION (NON-STRUCTURAL RP PROTEIN 7), FUNCTION (NON-STRUCTURAL PROTEIN 8), FUNCTION (RNA-DIRECTED RNA RP POLYMERASE), CATALYTIC ACTIVITY (RNA-DIRECTED RNA POLYMERASE), ACTIVITY RP REGULATION (RNA-DIRECTED RNA POLYMERASE), AND MUTAGENESIS OF SER-5253. 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 [11] {ECO:0000244|PDB:6YVA} 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 0:0-0(2020). RN [12] 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 0:0-0(2020). RN [13] 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). CC -!- FUNCTION: [Replicase polyprotein 1ab]: 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 interacting with the 40S ribosomal subunit (PubMed:32680882). Nsp1 C CC terminus binds to and obstructs ribosomal mRNA entry tunnel CC (PubMed:32680882). Thereby inhibits antiviral response triggered by CC innate immunity or interferons (PubMed:32680882). The nsp1-40S ribosome CC complex further induces an endonucleolytic cleavage near the 5'UTR of CC host mRNAs, targeting them for degradation (By similarity). Viral mRNAs CC are not susceptible to nsp1-mediated endonucleolytic RNA cleavage CC thanks to the presence of a 5'-end leader sequence and are therefore CC protected from degradation (By similarity). By suppressing host gene CC expression, nsp1 facilitates efficient viral gene expression in CC infected cells and evasion from host immune response (By similarity). CC {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:32680882}. 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: [Non-structural protein 3]: 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 substrates in CC vitro (PubMed:32726803). Can play a role in host ADP-ribosylation by CC binding ADP-ribose (PubMed:32578982). {ECO:0000250|UniProtKB:P0C6X7, CC ECO:0000269|PubMed:32578982, ECO:0000269|PubMed:32726803, CC ECO:0000269|PubMed:32733001}. 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]: Cleaves the C-terminus of replicase CC polyprotein at 11 sites (PubMed:32321856). Recognizes substrates CC containing the core sequence [ILMVF]-Q-|-[SGACN] (PubMed:32198291, CC PubMed:32272481). Also able to bind an ADP-ribose-1''-phosphate (ADRP) CC (By similarity) (PubMed:32198291, PubMed:32272481). CC {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:32198291, CC ECO:0000269|PubMed:32272481, ECO:0000269|PubMed:32321856}. CC -!- FUNCTION: [Non-structural protein 6]: Plays a role in the initial CC induction of autophagosomes from host reticulum endoplasmic. Later, CC limits the expansion of these phagosomes that are no longer able to CC deliver viral components to lysosomes. {ECO:0000250|UniProtKB:P0C6X7}. 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). {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 9]: May participate in viral CC replication by acting as a ssRNA-binding protein. CC {ECO:0000250|UniProtKB:P0C6X7}. 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 -!- FUNCTION: [RNA-directed RNA polymerase]: Responsible for replication CC and transcription of the viral RNA genome. CC {ECO:0000305|PubMed:32277040, ECO:0000305|PubMed:32358203, CC ECO:0000305|PubMed:32438371, ECO:0000305|PubMed:32526208}. CC -!- FUNCTION: [Helicase]: Multi-functional protein with a zinc-binding CC domain in N-terminus displaying RNA and DNA duplex-unwinding activities CC with 5' to 3' polarity. Activity of helicase is dependent on magnesium. CC {ECO:0000250|UniProtKB:P0C6X7}. CC -!- FUNCTION: [Proofreading exoribonuclease]: Enzyme possessing two CC different activities: an exoribonuclease activity acting on both ssRNA CC and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase CC activity. Acts as a proofreading exoribonuclease for RNA replication, CC thereby lowering The sensitivity of the virus to RNA mutagens. CC {ECO:0000250|UniProtKB:P0C6X7}. CC -!- FUNCTION: [Uridylate-specific endoribonuclease]: Mn(2+)-dependent, CC uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to CC the cleaved bond. {ECO:0000250|UniProtKB:P0C6X7}. CC -!- FUNCTION: [2'-O-methyltransferase]: Methyltransferase that mediates CC mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral CC mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. CC Therefore plays an essential role in viral mRNAs cap methylation which CC is essential to evade immune system. {ECO:0000250|UniProtKB:P0C6X7}. CC -!- CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:11128, Rhea:RHEA- CC COMP:11129, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:83400; CC EC=2.7.7.48; Evidence={ECO:0000269|PubMed:32358203, CC ECO:0000269|PubMed:32438371, ECO:0000269|PubMed:32526208}; CC -!- CATALYTIC ACTIVITY: [Helicase]: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; CC Evidence={ECO:0000250|UniProtKB:P0C6X7}; CC -!- CATALYTIC ACTIVITY: [Helicase]: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; CC Evidence={ECO:0000250|UniProtKB:P0C6X7}; CC -!- CATALYTIC ACTIVITY: [3C-like proteinase]: CC Reaction=TSAVLQ-|-SGFRK-NH(2) 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: [Non-structural protein 3]: 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 -!- ACTIVITY REGULATION: [Non-structural protein 3]: Inhibited in vitro by CC GRL-0617. {ECO:0000269|PubMed:32726803}. CC -!- ACTIVITY REGULATION: [Proofreading exoribonuclease]: Inhibited by CC Remdesivir antiviral drug (GS-5734). {ECO:0000250|UniProtKB:P0C6X7}. CC -!- ACTIVITY REGULATION: [RNA-directed RNA polymerase]: Inhibited by CC Remdesivir antiviral drug (GS-5734) through non-obligate RNA chain CC termination. {ECO:0000269|PubMed:32358203, CC ECO:0000269|PubMed:32526208}. CC -!- ACTIVITY REGULATION: [3C-like proteinase]: 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]: 3CL-PRO exists as monomer and homodimer. CC 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 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 -!- SUBUNIT: [RNA-directed RNA polymerase]: Interacts with nsp7 and nsp8. CC {ECO:0000269|PubMed:32277040, ECO:0000269|PubMed:32358203, CC ECO:0000269|PubMed:32438371, ECO:0000269|PubMed:32526208}. CC -!- SUBUNIT: [Proofreading exoribonuclease]: Interacts (via N-terminus) CC with DDX1. Interacts with nsp10. {ECO:0000250|UniProtKB:P0C6X7}. CC -!- SUBUNIT: [2'-O-methyltransferase]: Interacts with nsp10. CC {ECO:0000250|UniProtKB:P0C6X7}. CC -!- INTERACTION: CC PRO_0000449623; PRO_0000449623 [P0DTD1]: rep; NbExp=2; IntAct=EBI-25475864, EBI-25475864; CC PRO_0000449625; PRO_0000449626 [P0DTD1]: rep; NbExp=13; IntAct=EBI-25475871, EBI-25475874; CC PRO_0000449626; P04439: HLA-A; Xeno; NbExp=3; IntAct=EBI-25475874, EBI-1042870; CC PRO_0000449627; PRO_0000449627 [P0DTD1]: rep; NbExp=2; IntAct=EBI-25475877, EBI-25475877; CC PRO_0000449628; PRO_0000449633 [P0DTD1]: rep; NbExp=4; IntAct=EBI-25475880, EBI-25492395; CC PRO_0000449629; PRO_0000449626 [P0DTD1]: rep; NbExp=2; IntAct=EBI-25475885, EBI-25475874; CC -!- SUBCELLULAR LOCATION: [Non-structural protein 3]: 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: [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}. 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 8]: Host cytoplasm, host CC perinuclear region {ECO:0000250|UniProtKB:P0C6X9}. 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}. 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}. 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: [Helicase]: Host endoplasmic reticulum-Golgi CC intermediate compartment {ECO:0000250|UniProtKB:P0C6X7}. Note=The CC helicase interacts with the N protein in membranous complexes and CC colocalizes with sites of synthesis of new viral RNA. CC {ECO:0000250|UniProtKB:P0C6X9}. CC -!- SUBCELLULAR LOCATION: [Uridylate-specific endoribonuclease]: Host CC cytoplasm, host perinuclear region {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 1ab; CC IsoId=P0DTD1-1; Sequence=Displayed; CC Name=Replicase polyprotein 1a; CC IsoId=P0DTC1-1; 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:P0C6X7}. 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 -!- MISCELLANEOUS: [Replicase polyprotein 1ab]: Produced by -1 ribosomal CC frameshifting at the 1a-1b genes boundary. CC {ECO:0000250|UniProtKB:P0C6X7}. 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; -; Genomic_RNA. DR RefSeq; YP_009724389.1; NC_045512.2. DR PDB; 5R7Y; X-ray; 1.65 A; A=3264-3569. DR PDB; 5R7Z; X-ray; 1.59 A; A=3264-3569. DR PDB; 5R80; X-ray; 1.93 A; A=3264-3569. DR PDB; 5R81; X-ray; 1.95 A; A=3264-3569. DR PDB; 5R82; X-ray; 1.31 A; A=3264-3569. DR PDB; 5R83; X-ray; 1.58 A; A=3264-3569. DR PDB; 5R84; X-ray; 1.83 A; A=3264-3569. DR PDB; 5R8T; X-ray; 1.27 A; A=3264-3569. DR PDB; 5RE4; X-ray; 1.88 A; A=3264-3569. DR PDB; 5RE5; X-ray; 2.07 A; A=3264-3569. DR PDB; 5RE6; X-ray; 1.87 A; A=3264-3569. DR PDB; 5RE7; X-ray; 1.79 A; A=3264-3569. DR PDB; 5RE8; X-ray; 1.81 A; A=3264-3569. DR PDB; 5RE9; X-ray; 1.72 A; A=3264-3569. DR PDB; 5REA; X-ray; 1.63 A; A=3264-3569. DR PDB; 5REB; X-ray; 1.68 A; A=3264-3569. DR PDB; 5REC; X-ray; 1.73 A; A=3264-3569. DR PDB; 5RED; X-ray; 1.47 A; A=3264-3569. DR PDB; 5REE; X-ray; 1.77 A; A=3264-3569. DR PDB; 5REF; X-ray; 1.61 A; A=3264-3569. DR PDB; 5REG; X-ray; 1.67 A; A=3264-3569. DR PDB; 5REH; X-ray; 1.80 A; A=3264-3569. DR PDB; 5REI; X-ray; 1.82 A; A=3264-3569. DR PDB; 5REJ; X-ray; 1.72 A; A=3264-3569. DR PDB; 5REK; X-ray; 1.74 A; A=3264-3569. DR PDB; 5REL; X-ray; 1.62 A; A=3264-3569. DR PDB; 5REM; X-ray; 1.96 A; A=3264-3569. DR PDB; 5REN; X-ray; 2.15 A; A=3264-3569. DR PDB; 5REO; X-ray; 1.88 A; A=3264-3569. DR PDB; 5REP; X-ray; 1.81 A; A=3264-3569. DR PDB; 5RER; X-ray; 1.88 A; A=3264-3569. DR PDB; 5RES; X-ray; 1.65 A; A=3264-3569. DR PDB; 5RET; X-ray; 1.68 A; A=3264-3569. DR PDB; 5REU; X-ray; 1.69 A; A=3264-3569. DR PDB; 5REV; X-ray; 1.60 A; A=3264-3569. DR PDB; 5REW; X-ray; 1.55 A; A=3264-3569. DR PDB; 5REX; X-ray; 2.07 A; A=3264-3569. DR PDB; 5REY; X-ray; 1.96 A; A=3264-3569. DR PDB; 5REZ; X-ray; 1.79 A; A=3264-3569. DR PDB; 5RF0; X-ray; 1.65 A; A=3264-3569. DR PDB; 5RF1; X-ray; 1.73 A; A=3264-3569. DR PDB; 5RF2; X-ray; 1.53 A; A=3264-3569. DR PDB; 5RF3; X-ray; 1.50 A; A=3264-3569. DR PDB; 5RF4; X-ray; 1.61 A; A=3264-3569. DR PDB; 5RF5; X-ray; 1.74 A; A=3264-3569. DR PDB; 5RF6; X-ray; 1.45 A; A=3264-3569. DR PDB; 5RF7; X-ray; 1.54 A; A=3264-3569. DR PDB; 5RF8; X-ray; 1.44 A; A=3264-3569. DR PDB; 5RF9; X-ray; 1.43 A; A=3264-3569. DR PDB; 5RFA; X-ray; 1.52 A; A=3264-3569. DR PDB; 5RFB; X-ray; 1.48 A; A=3264-3569. DR PDB; 5RFC; X-ray; 1.40 A; A=3264-3569. DR PDB; 5RFD; X-ray; 1.41 A; A=3264-3569. DR PDB; 5RFE; X-ray; 1.46 A; A=3264-3569. DR PDB; 5RFF; X-ray; 1.78 A; A=3264-3569. DR PDB; 5RFG; X-ray; 2.32 A; A=3264-3569. DR PDB; 5RFH; X-ray; 1.58 A; A=3264-3569. DR PDB; 5RFI; X-ray; 1.69 A; A=3264-3569. DR PDB; 5RFJ; X-ray; 1.80 A; A=3264-3569. DR PDB; 5RFK; X-ray; 1.75 A; A=3264-3569. DR PDB; 5RFL; X-ray; 1.64 A; A=3264-3569. DR PDB; 5RFM; X-ray; 2.06 A; A=3264-3569. DR PDB; 5RFN; X-ray; 1.80 A; A=3264-3569. DR PDB; 5RFO; X-ray; 1.83 A; A=3264-3569. DR PDB; 5RFP; X-ray; 2.03 A; A=3264-3569. DR PDB; 5RFQ; X-ray; 1.76 A; A=3264-3569. DR PDB; 5RFR; X-ray; 1.71 A; A=3264-3569. DR PDB; 5RFS; X-ray; 1.70 A; A=3264-3569. DR PDB; 5RFT; X-ray; 1.58 A; A=3264-3569. DR PDB; 5RFU; X-ray; 1.53 A; A=3264-3569. DR PDB; 5RFV; X-ray; 1.48 A; A=3264-3569. DR PDB; 5RFW; X-ray; 1.43 A; A=3264-3569. DR PDB; 5RFX; X-ray; 1.55 A; A=3264-3569. DR PDB; 5RFY; X-ray; 1.90 A; A=3264-3569. DR PDB; 5RFZ; X-ray; 1.68 A; A=3264-3569. DR PDB; 5RG0; X-ray; 1.72 A; A=3264-3569. DR PDB; 5RG1; X-ray; 1.65 A; A=3264-3569. DR PDB; 5RG2; X-ray; 1.63 A; A=3264-3569. DR PDB; 5RG3; X-ray; 1.58 A; A=3264-3569. DR PDB; 5RGG; X-ray; 2.26 A; A=3264-3569. DR PDB; 5RGH; X-ray; 1.70 A; A=3264-3569. DR PDB; 5RGI; X-ray; 1.57 A; A=3264-3569. DR PDB; 5RGJ; X-ray; 1.34 A; A=3264-3569. DR PDB; 5RGK; X-ray; 1.43 A; A=3264-3569. DR PDB; 5RGL; X-ray; 1.76 A; A=3264-3569. DR PDB; 5RGM; X-ray; 2.04 A; A=3264-3569. DR PDB; 5RGN; X-ray; 1.86 A; A=3264-3569. DR PDB; 5RGO; X-ray; 1.74 A; A=3264-3569. DR PDB; 5RGP; X-ray; 2.07 A; A=3264-3569. DR PDB; 5RGQ; X-ray; 2.15 A; A=3264-3569. DR PDB; 5RGR; X-ray; 1.41 A; A=3264-3569. DR PDB; 5RGS; X-ray; 1.72 A; A=3264-3569. DR PDB; 5RGT; X-ray; 2.22 A; A=3264-3569. DR PDB; 5RGU; X-ray; 2.11 A; A=3264-3569. DR PDB; 5RGV; X-ray; 1.82 A; A=3264-3569. DR PDB; 5RGW; X-ray; 1.43 A; A=3264-3569. DR PDB; 5RGX; X-ray; 1.69 A; A=3264-3569. DR PDB; 5RGY; X-ray; 1.98 A; A=3264-3569. DR PDB; 5RGZ; X-ray; 1.52 A; A=3264-3569. DR PDB; 5RH0; X-ray; 1.92 A; A=3264-3569. DR PDB; 5RH1; X-ray; 1.96 A; A=3264-3569. DR PDB; 5RH2; X-ray; 1.83 A; A=3264-3569. DR PDB; 5RH3; X-ray; 1.69 A; A=3264-3569. DR PDB; 5RH4; X-ray; 1.34 A; A=3264-3569. DR PDB; 5RH5; X-ray; 1.72 A; A=3264-3569. DR PDB; 5RH6; X-ray; 1.60 A; A=3264-3569. DR PDB; 5RH7; X-ray; 1.71 A; A=3264-3569. DR PDB; 5RH8; X-ray; 1.81 A; A=3264-3569. DR PDB; 5RH9; X-ray; 1.91 A; A=3264-3569. DR PDB; 5RHA; X-ray; 1.51 A; A=3264-3569. DR PDB; 5RHB; X-ray; 1.43 A; A=3264-3569. DR PDB; 5RHC; X-ray; 1.58 A; A=3264-3569. DR PDB; 5RHD; X-ray; 1.57 A; A=3264-3569. DR PDB; 5RHE; X-ray; 1.56 A; A=3264-3569. DR PDB; 5RHF; X-ray; 1.76 A; A=3264-3569. DR PDB; 6LU7; X-ray; 2.16 A; A=3264-3569. DR PDB; 6LZE; X-ray; 1.50 A; A=3264-3566. DR PDB; 6M03; X-ray; 2.00 A; A=3264-3569. DR PDB; 6M0K; X-ray; 1.50 A; A=3264-3567. DR PDB; 6M2N; X-ray; 2.20 A; A/B/C/D=3264-3569. DR PDB; 6M2Q; X-ray; 1.70 A; A=3264-3569. DR PDB; 6M71; EM; 2.90 A; C=3860-3942, D=3943-4090, A=4393-5324. DR PDB; 6VWW; X-ray; 2.20 A; A/B=6453-6798. DR PDB; 6VXS; X-ray; 2.03 A; A/B=1024-1192. DR PDB; 6W01; X-ray; 1.90 A; A/B=6453-6798. DR PDB; 6W02; X-ray; 1.50 A; A/B=1024-1192. DR PDB; 6W4B; X-ray; 2.95 A; A/B=4141-4253. DR PDB; 6W4H; X-ray; 1.80 A; A=6799-7096, B=4254-4392. DR PDB; 6W61; X-ray; 2.00 A; B=4254-4392, A=6799-7096. DR PDB; 6W63; X-ray; 2.10 A; A=3264-3569. DR PDB; 6W6Y; X-ray; 1.45 A; A/B=1024-1192. DR PDB; 6W75; X-ray; 1.95 A; B/D=4254-4392, A/C=6799-7096. DR PDB; 6W9C; X-ray; 2.70 A; A/B/C=1564-1878. DR PDB; 6W9Q; X-ray; 2.05 A; A=4141-4253. DR PDB; 6WC1; X-ray; 2.40 A; A/B=4141-4253. DR PDB; 6WCF; X-ray; 1.06 A; A=1024-1192. DR PDB; 6WEN; X-ray; 1.35 A; A=1024-1192. DR PDB; 6WEY; X-ray; 0.95 A; A=1025-1195. DR PDB; 6WIQ; X-ray; 2.85 A; A=3860-3942, B=4019-4140. DR PDB; 6WJT; X-ray; 2.00 A; A/C=6799-7096, B/D=4254-4392. DR PDB; 6WKQ; X-ray; 1.98 A; A/C=6799-7096, B/D=4254-4392. DR PDB; 6WKS; X-ray; 1.80 A; AAA=6799-7096, BBB=4254-4392. DR PDB; 6WLC; X-ray; 1.82 A; A/B=6453-6798. DR PDB; 6WNP; X-ray; 1.44 A; A=3264-3569. DR PDB; 6WOJ; X-ray; 2.20 A; A/B/C/D=1023-1197. DR PDB; 6WQ3; X-ray; 2.10 A; A=6799-7096, B=4254-4392. DR PDB; 6WQD; X-ray; 1.95 A; A/C=3860-3942, B/D=4019-4140. DR PDB; 6WQF; X-ray; 2.30 A; A=3264-3569. DR PDB; 6WRH; X-ray; 1.60 A; A=1564-1878. DR PDB; 6WRZ; X-ray; 2.25 A; A=6799-7096, B=4254-4392. DR PDB; 6WTC; X-ray; 1.85 A; A/C=3860-3942, B/D=4019-4140. DR PDB; 6WTJ; X-ray; 1.90 A; A=3264-3569. DR PDB; 6WTK; X-ray; 2.00 A; A=3264-3569. DR PDB; 6WTM; X-ray; 1.85 A; A/B=3264-3569. DR PDB; 6WTT; X-ray; 2.15 A; A/B/C=3264-3567. DR PDB; 6WUU; X-ray; 2.79 A; A/B/C/D=1562-1879. DR PDB; 6WVN; X-ray; 2.00 A; A=6799-7096, B=4254-4392. DR PDB; 6WX4; X-ray; 1.66 A; D=1562-1879. DR PDB; 6WXC; X-ray; 1.85 A; A/B=6453-6798. DR PDB; 6WXD; X-ray; 2.00 A; A/B=4141-4253. DR PDB; 6WZU; X-ray; 1.79 A; A=1564-1878. DR PDB; 6X1B; X-ray; 1.97 A; A/B=6453-6798. DR PDB; 6X4I; X-ray; 1.85 A; A/B=6453-6798. DR PDB; 6XA4; X-ray; 1.65 A; A=3264-3569. DR PDB; 6XA9; X-ray; 2.90 A; A/C/E=1563-1878. DR PDB; 6XAA; X-ray; 2.70 A; A=1563-1878. DR PDB; 6XB0; X-ray; 1.80 A; A=3264-3569. DR PDB; 6XB1; X-ray; 1.80 A; A=3264-3569. DR PDB; 6XB2; X-ray; 2.10 A; A=3264-3569. DR PDB; 6XBG; X-ray; 1.45 A; A/B=3264-3569. DR PDB; 6XBH; X-ray; 1.60 A; A=3264-3569. DR PDB; 6XBI; X-ray; 1.70 A; A/B=3264-3569. DR PDB; 6XCH; X-ray; 2.20 A; A=3264-3569. DR PDB; 6XDH; X-ray; 2.35 A; A/B=6453-6798. DR PDB; 6XFN; X-ray; 1.70 A; A=3264-3569. DR PDB; 6XG3; X-ray; 2.48 A; A=1564-1878. DR PDB; 6XHM; X-ray; 1.41 A; A/B=3264-3569. DR PDB; 6XHU; X-ray; 1.80 A; A/C=3264-3569. DR PDB; 6XIP; X-ray; 1.50 A; A/C=3860-3942, B/D=4019-4140. DR PDB; 6XKF; X-ray; 1.80 A; A/B=3264-3569. DR PDB; 6XKH; X-ray; 1.28 A; A=3264-3569. DR PDB; 6XKM; X-ray; 2.25 A; A=6799-7096, B=4254-4392. DR PDB; 6XMK; X-ray; 1.70 A; A/B=3264-3568. DR PDB; 6XOA; X-ray; 2.10 A; A/B/C/D=3264-3569. DR PDB; 6XQS; X-ray; 1.90 A; A=3264-3569. DR PDB; 6XQT; X-ray; 2.30 A; A/B=3264-3569. DR PDB; 6XQU; X-ray; 2.20 A; A=3264-3569. DR PDB; 6XR3; X-ray; 1.45 A; A=3264-3569. 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; 6Y84; X-ray; 1.39 A; A=3264-3569. DR PDB; 6YB7; X-ray; 1.25 A; A=3264-3569. DR PDB; 6YNQ; X-ray; 1.80 A; A=3264-3569. DR PDB; 6YT8; X-ray; 2.05 A; A=3264-3569. DR PDB; 6YVA; X-ray; 3.18 A; A=1564-1878. DR PDB; 6YVF; X-ray; 1.60 A; A=3264-3569. DR PDB; 6YWK; X-ray; 2.20 A; A/B/C/D/E=1025-1194. DR PDB; 6YWL; X-ray; 2.50 A; A/B/C/D/E=1025-1194. DR PDB; 6YWM; X-ray; 2.16 A; A/B/C=1025-1194. DR PDB; 6YYT; EM; 2.90 A; A=4424-5321, B=3948-4133, C=3860-3932. DR PDB; 6YZ1; X-ray; 2.40 A; A=6798-7096, B=4263-4384. DR PDB; 6YZ6; X-ray; 1.70 A; A=3264-3569. DR PDB; 6Z2E; X-ray; 1.70 A; AAA=3264-3569. DR PDB; 6ZCT; X-ray; 2.55 A; A=4263-4384. DR PDB; 6ZLW; EM; 2.60 A; i=1-180. DR PDB; 6ZM7; EM; 2.70 A; CF=1-180. DR PDB; 6ZME; EM; 3.00 A; CF=1-180. DR PDB; 6ZMI; EM; 2.60 A; i=1-180. DR PDB; 6ZMO; EM; 3.10 A; i=1-180. DR PDB; 6ZMT; EM; 3.00 A; i=1-180. DR PDB; 6ZN5; EM; 3.20 A; i=1-180. DR PDB; 6ZOJ; EM; 2.80 A; j=1-180. DR PDB; 6ZOK; EM; 2.80 A; j=1-180. DR PDB; 6ZON; EM; 3.00 A; J=1-180. DR PDB; 6ZP4; EM; 2.90 A; J=1-180. DR PDB; 6ZRT; X-ray; 2.10 A; A=3264-3569. DR PDB; 6ZRU; X-ray; 2.10 A; A=3264-3569. DR PDB; 6ZSL; X-ray; 1.94 A; A/B=5325-5925. DR PDB; 7BQ7; X-ray; 2.37 A; A=6799-7096, B=4254-4392. DR PDB; 7BQY; X-ray; 1.70 A; A=3264-3569. DR PDB; 7BRO; X-ray; 2.00 A; A=3264-3569. DR PDB; 7BRP; X-ray; 1.80 A; A/B=3264-3569. DR PDB; 7BRR; X-ray; 1.40 A; A/B=3264-3569. DR PDB; 7BTF; EM; 2.95 A; A=4393-5324, B=3943-4090, C=3860-3942. DR PDB; 7BUY; X-ray; 1.60 A; A=3264-3569. DR PDB; 7BV1; EM; 2.80 A; C=3860-3942, B=3943-4140, A=4393-5324. DR PDB; 7BV2; EM; 2.50 A; C=3860-3942, B=3943-4140, A=4393-5324. DR PDB; 7BZF; EM; 3.26 A; A=4393-5324, B=3943-4140, D=3943-4140, E=3860-3942. DR PDB; 7C2I; X-ray; 2.50 A; A=6799-7096, B=4254-4392. DR PDB; 7C2J; X-ray; 2.80 A; A=6799-7096, B=4254-4392. DR PDB; 7C2K; EM; 2.93 A; A=4393-5324, B=3943-4140, D=3943-4140, E=3860-3942. DR PDB; 7C2Q; X-ray; 1.93 A; A/B=3266-3561. DR PDB; 7C2Y; X-ray; 1.91 A; A/B=3264-3561. DR PDB; 7C6S; X-ray; 1.60 A; A=3264-3569. DR PDB; 7C6U; X-ray; 2.00 A; A=3264-3569. DR PDB; 7C7P; X-ray; 1.74 A; A/B=3264-3569. DR PDB; 7C8B; X-ray; 2.20 A; A=3264-3569. DR PDB; 7C8R; X-ray; 2.30 A; A=3264-3569. DR PDB; 7C8T; X-ray; 2.05 A; A=3264-3569. DR PDB; 7C8U; X-ray; 2.35 A; A=3264-3569. DR PDB; 7CBT; X-ray; 2.35 A; A/B=3264-3569. DR PDB; 7CJD; X-ray; 2.50 A; A/B/C/D=1564-1881. DR PDB; 7CJM; X-ray; 3.20 A; B=1564-1878. DR PDB; 7CMD; X-ray; 2.59 A; A/B/C/D=1564-1881. DR PDB; 7COM; X-ray; 2.25 A; A/B=3264-3569. DR PDB; 7JFQ; X-ray; 1.55 A; A=3264-3569. DR PDB; 7JHE; X-ray; 2.25 A; A=6799-7096, B=4254-4392. DR PDB; 7JIB; X-ray; 2.65 A; A=6799-7096, B=4254-4392. DR PDB; 7JME; X-ray; 1.55 A; A=1025-1195. DR PDB; 7JPE; X-ray; 2.18 A; A=6799-7096, B=4254-4392. DR PDB; 7JR3; X-ray; 1.55 A; A=3264-3569. DR PDB; 7JR4; X-ray; 1.55 A; A=3264-3569. DR PDB; 7JU7; X-ray; 1.60 A; A=3264-3569. DR PDB; 7JUN; Other; 2.30 A; A=3264-3569. DR PDB; 7JYC; X-ray; 1.79 A; A=3264-3569. DR PDBsum; 5R7Y; -. DR PDBsum; 5R7Z; -. DR PDBsum; 5R80; -. DR PDBsum; 5R81; -. DR PDBsum; 5R82; -. DR PDBsum; 5R83; -. DR PDBsum; 5R84; -. DR PDBsum; 5R8T; -. DR PDBsum; 5RE4; -. DR PDBsum; 5RE5; -. DR PDBsum; 5RE6; -. DR PDBsum; 5RE7; -. DR PDBsum; 5RE8; -. DR PDBsum; 5RE9; -. DR PDBsum; 5REA; -. DR PDBsum; 5REB; -. DR PDBsum; 5REC; -. DR PDBsum; 5RED; -. DR PDBsum; 5REE; -. DR PDBsum; 5REF; -. DR PDBsum; 5REG; -. DR PDBsum; 5REH; -. DR PDBsum; 5REI; -. DR PDBsum; 5REJ; -. DR PDBsum; 5REK; -. DR PDBsum; 5REL; -. DR PDBsum; 5REM; -. DR PDBsum; 5REN; -. DR PDBsum; 5REO; -. DR PDBsum; 5REP; -. DR PDBsum; 5RER; -. DR PDBsum; 5RES; -. DR PDBsum; 5RET; -. DR PDBsum; 5REU; -. DR PDBsum; 5REV; -. DR PDBsum; 5REW; -. DR PDBsum; 5REX; -. DR PDBsum; 5REY; -. DR PDBsum; 5REZ; -. DR PDBsum; 5RF0; -. DR PDBsum; 5RF1; -. DR PDBsum; 5RF2; -. DR PDBsum; 5RF3; -. DR PDBsum; 5RF4; -. DR PDBsum; 5RF5; -. DR PDBsum; 5RF6; -. DR PDBsum; 5RF7; -. DR PDBsum; 5RF8; -. DR PDBsum; 5RF9; -. DR PDBsum; 5RFA; -. DR PDBsum; 5RFB; -. DR PDBsum; 5RFC; -. DR PDBsum; 5RFD; -. DR PDBsum; 5RFE; -. DR PDBsum; 5RFF; -. DR PDBsum; 5RFG; -. DR PDBsum; 5RFH; -. DR PDBsum; 5RFI; -. DR PDBsum; 5RFJ; -. DR PDBsum; 5RFK; -. DR PDBsum; 5RFL; -. DR PDBsum; 5RFM; -. DR PDBsum; 5RFN; -. DR PDBsum; 5RFO; -. DR PDBsum; 5RFP; -. DR PDBsum; 5RFQ; -. DR PDBsum; 5RFR; -. DR PDBsum; 5RFS; -. DR PDBsum; 5RFT; -. DR PDBsum; 5RFU; -. DR PDBsum; 5RFV; -. DR PDBsum; 5RFW; -. DR PDBsum; 5RFX; -. DR PDBsum; 5RFY; -. DR PDBsum; 5RFZ; -. DR PDBsum; 5RG0; -. DR PDBsum; 5RG1; -. DR PDBsum; 5RG2; -. DR PDBsum; 5RG3; -. DR PDBsum; 5RGG; -. DR PDBsum; 5RGH; -. DR PDBsum; 5RGI; -. DR PDBsum; 5RGJ; -. DR PDBsum; 5RGK; -. DR PDBsum; 5RGL; -. DR PDBsum; 5RGM; -. DR PDBsum; 5RGN; -. DR PDBsum; 5RGO; -. DR PDBsum; 5RGP; -. DR PDBsum; 5RGQ; -. DR PDBsum; 5RGR; -. DR PDBsum; 5RGS; -. DR PDBsum; 5RGT; -. DR PDBsum; 5RGU; -. DR PDBsum; 5RGV; -. DR PDBsum; 5RGW; -. DR PDBsum; 5RGX; -. DR PDBsum; 5RGY; -. DR PDBsum; 5RGZ; -. DR PDBsum; 5RH0; -. DR PDBsum; 5RH1; -. DR PDBsum; 5RH2; -. DR PDBsum; 5RH3; -. DR PDBsum; 5RH4; -. DR PDBsum; 5RH5; -. DR PDBsum; 5RH6; -. DR PDBsum; 5RH7; -. DR PDBsum; 5RH8; -. DR PDBsum; 5RH9; -. DR PDBsum; 5RHA; -. DR PDBsum; 5RHB; -. DR PDBsum; 5RHC; -. DR PDBsum; 5RHD; -. DR PDBsum; 5RHE; -. DR PDBsum; 5RHF; -. DR PDBsum; 6LU7; -. DR PDBsum; 6LZE; -. DR PDBsum; 6M03; -. DR PDBsum; 6M0K; -. DR PDBsum; 6M2N; -. DR PDBsum; 6M2Q; -. DR PDBsum; 6M71; -. DR PDBsum; 6VWW; -. DR PDBsum; 6VXS; -. DR PDBsum; 6W01; -. DR PDBsum; 6W02; -. DR PDBsum; 6W4B; -. DR PDBsum; 6W4H; -. DR PDBsum; 6W61; -. DR PDBsum; 6W63; -. DR PDBsum; 6W6Y; -. DR PDBsum; 6W75; -. DR PDBsum; 6W9C; -. DR PDBsum; 6W9Q; -. DR PDBsum; 6WC1; -. DR PDBsum; 6WCF; -. DR PDBsum; 6WEN; -. DR PDBsum; 6WEY; -. DR PDBsum; 6WIQ; -. DR PDBsum; 6WJT; -. DR PDBsum; 6WKQ; -. DR PDBsum; 6WKS; -. DR PDBsum; 6WLC; -. DR PDBsum; 6WNP; -. DR PDBsum; 6WOJ; -. DR PDBsum; 6WQ3; -. DR PDBsum; 6WQD; -. DR PDBsum; 6WQF; -. DR PDBsum; 6WRH; -. DR PDBsum; 6WRZ; -. DR PDBsum; 6WTC; -. DR PDBsum; 6WTJ; -. DR PDBsum; 6WTK; -. DR PDBsum; 6WTM; -. DR PDBsum; 6WTT; -. DR PDBsum; 6WUU; -. DR PDBsum; 6WVN; -. DR PDBsum; 6WX4; -. DR PDBsum; 6WXC; -. DR PDBsum; 6WXD; -. DR PDBsum; 6WZU; -. DR PDBsum; 6X1B; -. DR PDBsum; 6X4I; -. DR PDBsum; 6XA4; -. DR PDBsum; 6XA9; -. DR PDBsum; 6XAA; -. DR PDBsum; 6XB0; -. DR PDBsum; 6XB1; -. DR PDBsum; 6XB2; -. DR PDBsum; 6XBG; -. DR PDBsum; 6XBH; -. DR PDBsum; 6XBI; -. DR PDBsum; 6XCH; -. DR PDBsum; 6XDH; -. DR PDBsum; 6XFN; -. DR PDBsum; 6XG3; -. DR PDBsum; 6XHM; -. DR PDBsum; 6XHU; -. DR PDBsum; 6XIP; -. DR PDBsum; 6XKF; -. DR PDBsum; 6XKH; -. DR PDBsum; 6XKM; -. DR PDBsum; 6XMK; -. DR PDBsum; 6XOA; -. DR PDBsum; 6XQS; -. DR PDBsum; 6XQT; -. DR PDBsum; 6XQU; -. DR PDBsum; 6XR3; -. DR PDBsum; 6Y2E; -. DR PDBsum; 6Y2F; -. DR PDBsum; 6Y2G; -. DR PDBsum; 6Y84; -. DR PDBsum; 6YB7; -. DR PDBsum; 6YNQ; -. DR PDBsum; 6YT8; -. DR PDBsum; 6YVA; -. DR PDBsum; 6YVF; -. DR PDBsum; 6YWK; -. DR PDBsum; 6YWL; -. DR PDBsum; 6YWM; -. DR PDBsum; 6YYT; -. DR PDBsum; 6YZ1; -. DR PDBsum; 6YZ6; -. DR PDBsum; 6Z2E; -. DR PDBsum; 6ZCT; -. DR PDBsum; 6ZLW; -. DR PDBsum; 6ZM7; -. DR PDBsum; 6ZME; -. DR PDBsum; 6ZMI; -. DR PDBsum; 6ZMO; -. DR PDBsum; 6ZMT; -. DR PDBsum; 6ZN5; -. DR PDBsum; 6ZOJ; -. DR PDBsum; 6ZOK; -. DR PDBsum; 6ZON; -. DR PDBsum; 6ZP4; -. DR PDBsum; 6ZRT; -. DR PDBsum; 6ZRU; -. DR PDBsum; 6ZSL; -. DR PDBsum; 7BQ7; -. DR PDBsum; 7BQY; -. DR PDBsum; 7BRO; -. DR PDBsum; 7BRP; -. DR PDBsum; 7BRR; -. DR PDBsum; 7BTF; -. DR PDBsum; 7BUY; -. DR PDBsum; 7BV1; -. DR PDBsum; 7BV2; -. DR PDBsum; 7BZF; -. DR PDBsum; 7C2I; -. DR PDBsum; 7C2J; -. DR PDBsum; 7C2K; -. DR PDBsum; 7C2Q; -. DR PDBsum; 7C2Y; -. DR PDBsum; 7C6S; -. DR PDBsum; 7C6U; -. DR PDBsum; 7C7P; -. DR PDBsum; 7C8B; -. DR PDBsum; 7C8R; -. DR PDBsum; 7C8T; -. DR PDBsum; 7C8U; -. DR PDBsum; 7CBT; -. DR PDBsum; 7CJD; -. DR PDBsum; 7CJM; -. DR PDBsum; 7CMD; -. DR PDBsum; 7COM; -. DR PDBsum; 7JFQ; -. DR PDBsum; 7JHE; -. DR PDBsum; 7JIB; -. DR PDBsum; 7JME; -. DR PDBsum; 7JPE; -. DR PDBsum; 7JR3; -. DR PDBsum; 7JR4; -. DR PDBsum; 7JU7; -. DR PDBsum; 7JUN; -. DR PDBsum; 7JYC; -. DR SMR; P0DTD1; -. DR BioGRID; 4383850; 13. DR BioGRID; 4383851; 27. DR BioGRID; 4383852; 32. DR BioGRID; 4383853; 61. DR BioGRID; 4383854; 9. DR BioGRID; 4383855; 85. DR BioGRID; 4383856; 54. DR BioGRID; 4383857; 61. DR BioGRID; 4383858; 27. DR BioGRID; 4383859; 36. DR BioGRID; 4383860; 42. DR BioGRID; 4383861; 67. DR BioGRID; 4383862; 29. DR BioGRID; 4383863; 62. DR BioGRID; 4383864; 4. DR ComplexPortal; CPX-5685; SARS-CoV-2 main protease complex. DR ComplexPortal; CPX-5687; SARS-CoV-2 NSP9 complex. DR ComplexPortal; CPX-5688; SARS-CoV-2 NSP10-NSP16 2'-O-methyltransferase complex. DR ComplexPortal; CPX-5689; SARS-CoV-2 NSP15 complex. DR ComplexPortal; CPX-5690; SARS-CoV-2 primase complex. DR ComplexPortal; CPX-5691; SARS-CoV-2 NSP3-NSP4-NSP6 complex. DR ComplexPortal; CPX-5692; SARS-CoV-2 3'-5' exoribonuclease proof-reading complex. DR ComplexPortal; CPX-5742; SARS-CoV-2 polymerase complex. DR IntAct; P0DTD1; 427. DR GeneID; 43740578; -. DR Proteomes; UP000464024; Genome. DR GO; GO:0039714; C:cytoplasmic viral factory; ISS:UniProtKB. DR GO; GO:0030430; C:host cell cytoplasm; ISS:UniProtKB. DR GO; GO:0044172; C:host cell endoplasmic reticulum-Golgi intermediate compartment; IEA:UniProtKB-SubCell. DR GO; GO:0033644; C:host cell membrane; 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:0000175; F:3'-5'-exoribonuclease activity; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. 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:0003678; F:DNA helicase activity; IEA:UniProtKB-EC. DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW. DR GO; GO:0004527; F:exonuclease activity; IEA:UniProtKB-KW. DR GO; GO:0004386; F:helicase activity; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0019785; F:ISG15-specific protease activity; ISS:UniProtKB. DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW. DR GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; ISS:UniProtKB. DR GO; GO:0046983; F:protein dimerization activity; ISS:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC. DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; ISS:UniProtKB. DR GO; GO:0003727; F:single-stranded RNA binding; ISS:UniProtKB. DR GO; GO:0004843; F:thiol-dependent ubiquitin-specific protease activity; IEA:UniProtKB-EC. 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: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:0080009; P:mRNA methylation; 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:0090503; P:RNA phosphodiester bond hydrolysis, exonucleolytic; ISS:UniProtKB. DR GO; GO:0039548; P:suppression by virus of host IRF3 activity; ISS:UniProtKB. DR GO; GO:0039579; P:suppression by virus of host ISG15 activity; ISS:UniProtKB. DR GO; GO:0039644; P:suppression by virus of host NF-kappaB transcription factor activity; 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:0006351; P:transcription, DNA-templated; IEA:InterPro. DR GO; GO:0001172; P:transcription, RNA-templated; 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 GO; GO:0019083; P:viral transcription; ISS:UniProtKB. DR CDD; cd15239; 7tm_YRO2_fungal-like; 1. DR CDD; cd18808; SF1_C_Upf1; 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; 2.20.25.360; -; 1. DR Gene3D; 2.30.30.590; -; 1. DR Gene3D; 2.40.10.10; -; 2. DR Gene3D; 2.40.10.250; -; 1. DR Gene3D; 2.40.10.290; -; 1. DR Gene3D; 3.10.20.350; -; 1. DR Gene3D; 3.10.20.540; -; 1. DR Gene3D; 3.40.220.10; -; 1. DR Gene3D; 3.40.220.20; -; 1. DR Gene3D; 3.40.220.30; -; 1. DR Gene3D; 3.40.50.11020; -; 1. DR Gene3D; 3.40.50.11580; -; 1. DR Gene3D; 3.90.70.90; -; 1. DR InterPro; IPR027351; (+)RNA_virus_helicase_core_dom. DR InterPro; IPR043609; CoV_NSP15_C. DR InterPro; IPR043608; CoV_NSP15_M. DR InterPro; IPR043606; CoV_NSP15_N. DR InterPro; IPR043613; CoV_NSP2_C. DR InterPro; IPR043615; CoV_NSP2_N. DR InterPro; IPR043611; CoV_NSP3_C. DR InterPro; IPR043612; CoV_NSP4_N. DR InterPro; IPR043610; CoV_NSP6. DR InterPro; IPR043502; DNA/RNA_pol_sf. DR InterPro; IPR041679; DNA2/NAM7-like_C. DR InterPro; IPR022733; DPUP_SUD_C_bCoV. DR InterPro; IPR037227; EndoU-like. DR InterPro; IPR002589; Macro_dom. DR InterPro; IPR043472; Macro_dom-like. DR InterPro; IPR042570; NAR_sf. DR InterPro; IPR036333; NSP10_sf_CoV. DR InterPro; IPR009466; NSP14_CoV. DR InterPro; IPR043174; NSP15_middle_sf. DR InterPro; IPR042515; NSP15_N_CoV. DR InterPro; IPR009461; NSP16_CoV-like. DR InterPro; IPR021590; NSP1_bCoV. DR InterPro; IPR038030; NSP1_sf_bCoV. DR InterPro; IPR024375; NSP3_bCoV. DR InterPro; IPR024358; NSP3_N_bCoV. DR InterPro; IPR032592; NSP3_NAR_bCoV. DR InterPro; IPR038166; NSP3_PL2pro_sf_CoV. DR InterPro; IPR038400; NSP3_SUD-M_sf_bCoV. DR InterPro; IPR043478; NSP3_SUD-N_bCoV. DR InterPro; IPR038083; NSP3A-like. DR InterPro; IPR032505; NSP4_C_CoV. DR InterPro; IPR038123; NSP4_C_sf_CoV. DR InterPro; IPR014828; NSP7_CoV. DR InterPro; IPR037204; NSP7_sf_CoV. DR InterPro; IPR014829; NSP8_CoV-like. DR InterPro; IPR037230; NSP8_sf_CoV. DR InterPro; IPR014822; NSP9_CoV. DR InterPro; IPR036499; NSP9_sf_CoV. DR InterPro; IPR027417; P-loop_NTPase. 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; IPR001205; RNA-dir_pol_C. DR InterPro; IPR009469; RNA_pol_N_coronovir. DR InterPro; IPR018995; RNA_synth_NSP10_CoV. DR InterPro; IPR029063; SAM-dependent_MTases. DR InterPro; IPR043476; Yro2-like_7TM. 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; PF06471; CoV_Methyltr_1; 1. DR Pfam; PF06460; CoV_Methyltr_2; 1. DR Pfam; PF09401; CoV_NSP10; 1. DR Pfam; PF19215; CoV_NSP15_C; 1. DR Pfam; PF19216; CoV_NSP15_M; 1. DR Pfam; PF19219; CoV_NSP15_N; 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; PF06478; CoV_RPol_N; 1. DR Pfam; PF01661; Macro; 1. DR Pfam; PF05409; Peptidase_C30; 1. DR Pfam; PF00680; RdRP_1; 1. DR Pfam; PF01443; Viral_helicase1; 1. DR SMART; SM00506; A1pp; 1. DR SUPFAM; SSF101816; SSF101816; 1. DR SUPFAM; SSF140367; SSF140367; 1. DR SUPFAM; SSF142877; SSF142877; 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; SSF52540; SSF52540; 1. DR SUPFAM; SSF52949; SSF52949; 1. DR SUPFAM; SSF53335; SSF53335; 1. DR SUPFAM; SSF56672; SSF56672; 1. DR PROSITE; PS00867; CPSASE_2; 1. DR PROSITE; PS51653; CV_ZBD; 1. DR PROSITE; PS00213; LIPOCALIN; 1. DR PROSITE; PS51442; M_PRO; 1. DR PROSITE; PS51154; MACRO; 1. DR PROSITE; PS51124; PEPTIDASE_C16; 1. DR PROSITE; PS51657; PSRV_HELICASE; 1. DR PROSITE; PS50507; RDRP_SSRNA_POS; 1. PE 1: Evidence at protein level; KW 3D-structure; Activation of host autophagy by virus; ATP-binding; KW Decay of host mRNAs by virus; Endonuclease; KW Eukaryotic host gene expression shutoff by virus; KW Eukaryotic host translation shutoff by virus; Exonuclease; Helicase; KW Host cytoplasm; Host gene expression shutoff by virus; 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 ISG15 by virus; Inhibition of host NF-kappa-B by virus; KW Leucine-rich repeat; Membrane; Metal-binding; Methyltransferase; KW Modulation of host ubiquitin pathway by viral deubiquitinase; KW Modulation of host ubiquitin pathway by virus; Nuclease; KW Nucleotide-binding; Nucleotidyltransferase; Protease; Reference proteome; KW Repeat; Ribosomal frameshifting; RNA-binding; RNA-directed RNA polymerase; KW Thiol protease; Transferase; Transmembrane; Transmembrane helix; KW Ubl conjugation pathway; Viral immunoevasion; Viral RNA replication; Zinc; KW Zinc-finger. FT CHAIN 1..7096 FT /note="Replicase polyprotein 1ab" FT /id="PRO_0000449618" FT CHAIN 1..180 FT /note="Host translation inhibitor nsp1" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449619" FT CHAIN 181..818 FT /note="Non-structural protein 2" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449620" FT CHAIN 819..2763 FT /note="Non-structural protein 3" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449621" FT CHAIN 2764..3263 FT /note="Non-structural protein 4" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449622" FT CHAIN 3264..3569 FT /note="3C-like proteinase" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449623" FT CHAIN 3570..3859 FT /note="Non-structural protein 6" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449624" FT CHAIN 3860..3942 FT /note="Non-structural protein 7" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449625" FT CHAIN 3943..4140 FT /note="Non-structural protein 8" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449626" FT CHAIN 4141..4253 FT /note="Non-structural protein 9" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449627" FT CHAIN 4254..4392 FT /note="Non-structural protein 10" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449628" FT CHAIN 4393..5324 FT /note="RNA-directed RNA polymerase" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449629" FT CHAIN 5325..5925 FT /note="Helicase" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449630" FT CHAIN 5926..6452 FT /note="Proofreading exoribonuclease" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449631" FT CHAIN 6453..6798 FT /note="Uridylate-specific endoribonuclease" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449632" FT CHAIN 6799..7096 FT /note="2'-O-methyltransferase" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT /id="PRO_0000449633" 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" FT TRANSMEM 3587..3607 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 3608 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 3609..3629 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 3630..3634 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 3635..3655 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 3656..3673 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 3674..3694 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 3695..3729 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 3730..3750 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 3751..3778 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 3779..3799 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 3800..7096 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REPEAT 545..569 FT /note="LRR 1" FT /evidence="ECO:0000255" FT REPEAT 697..719 FT /note="LRR 2" FT /evidence="ECO:0000255" FT DOMAIN 1025..1194 FT /note="Macro" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490" FT DOMAIN 1634..1898 FT /note="Peptidase C16" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444" FT REPEAT 1680..1702 FT /note="LRR 3" FT /evidence="ECO:0000255" FT REPEAT 3185..3206 FT /note="LRR 4" FT /evidence="ECO:0000255" FT DOMAIN 3264..3569 FT /note="Peptidase C30" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00772" FT REPEAT 3935..3959 FT /note="LRR 5" FT /evidence="ECO:0000255" FT REPEAT 3977..4004 FT /note="LRR 6" FT /evidence="ECO:0000255" FT REPEAT 4591..4616 FT /note="LRR 7" FT /evidence="ECO:0000255" FT DOMAIN 5004..5166 FT /note="RdRp catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539" FT DOMAIN 5325..5408 FT /note="CV ZBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986" FT REPEAT 5552..5572 FT /note="LRR 8" FT /evidence="ECO:0000255" FT DOMAIN 5581..5762 FT /note="(+)RNA virus helicase ATP-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990" FT DOMAIN 5763..5932 FT /note="(+)RNA virus helicase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990" FT REPEAT 6817..6841 FT /note="LRR 9" FT /evidence="ECO:0000255" FT ZN_FING 1752..1789 FT /note="C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444" FT NP_BIND 5606..5613 FT /note="NTP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990" FT REGION 154..180 FT /note="Binding to 40s ribosome mRNA entry channel" FT /evidence="ECO:0000269|PubMed:32680882" FT REGION 4937..4947 FT /note="Interaction with RMP Remdesivir" FT /evidence="ECO:0000269|PubMed:32358203" 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:0000305|PubMed:32198291" FT ACT_SITE 3408 FT /note="Nucleophile; for 3CL-PRO activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00772, FT ECO:0000269|PubMed:32198291" FT METAL 4687 FT /note="Zinc 1; structural" FT /evidence="ECO:0000269|PubMed:32358203, FT ECO:0000269|PubMed:32526208" FT METAL 4693 FT /note="Zinc 1; structural" FT /evidence="ECO:0000269|PubMed:32358203, FT ECO:0000269|PubMed:32526208" FT METAL 4698 FT /note="Zinc 1; structural" FT /evidence="ECO:0000269|PubMed:32358203, FT ECO:0000269|PubMed:32526208" FT METAL 4702 FT /note="Zinc 1; structural" FT /evidence="ECO:0000269|PubMed:32358203, FT ECO:0000269|PubMed:32526208" FT METAL 4879 FT /note="Zinc 2; structural" FT /evidence="ECO:0000269|PubMed:32358203, FT ECO:0000269|PubMed:32526208" FT METAL 5034 FT /note="Zinc 2; structural" FT /evidence="ECO:0000269|PubMed:32358203, FT ECO:0000269|PubMed:32526208" FT METAL 5037 FT /note="Zinc 2; structural" FT /evidence="ECO:0000269|PubMed:32358203, FT ECO:0000269|PubMed:32526208" FT METAL 5038 FT /note="Zinc 2; structural" FT /evidence="ECO:0000269|PubMed:32358203, FT ECO:0000269|PubMed:32526208" FT METAL 5329 FT /note="Zinc 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986" FT METAL 5332 FT /note="Zinc 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986" FT METAL 5340 FT /note="Zinc 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986" FT METAL 5343 FT /note="Zinc 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986" FT METAL 5350 FT /note="Zinc 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986" FT METAL 5353 FT /note="Zinc 4; via tele nitrogen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986" FT METAL 5357 FT /note="Zinc 4; via pros nitrogen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986" FT METAL 5363 FT /note="Zinc 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986" FT METAL 5374 FT /note="Zinc 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986" FT METAL 5379 FT /note="Zinc 5; via pros nitrogen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986" FT METAL 5396 FT /note="Zinc 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986" FT METAL 5399 FT /note="Zinc 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00986" 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 SITE 5324..5325 FT /note="Cleavage; by 3CL-PRO" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT SITE 5925..5926 FT /note="Cleavage; by 3CL-PRO" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT SITE 6452..6453 FT /note="Cleavage; by 3CL-PRO" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" FT SITE 6798..6799 FT /note="Cleavage; by 3CL-PRO" FT /evidence="ECO:0000250|UniProtKB:P0C6V3" 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 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->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 5253 FT /note="S->A: Reduces RdRp inhibition by remdesivir." FT /evidence="ECO:0000269|PubMed:32526208" FT HELIX 153..160 FT /evidence="ECO:0000244|PDB:6ZOJ" FT HELIX 166..178 FT /evidence="ECO:0000244|PDB:6ZOJ" FT STRAND 1032..1042 FT /evidence="ECO:0000244|PDB:6WEY" FT HELIX 1045..1052 FT /evidence="ECO:0000244|PDB:6WEY" FT STRAND 1055..1060 FT /evidence="ECO:0000244|PDB:6WEY" FT HELIX 1070..1078 FT /evidence="ECO:0000244|PDB:6WEY" FT TURN 1079..1081 FT /evidence="ECO:0000244|PDB:6WEY" FT HELIX 1082..1094 FT /evidence="ECO:0000244|PDB:6WEY" FT STRAND 1102..1106 FT /evidence="ECO:0000244|PDB:6WEY" FT TURN 1108..1110 FT /evidence="ECO:0000244|PDB:6WEY" FT STRAND 1112..1117 FT /evidence="ECO:0000244|PDB:6WEY" FT HELIX 1122..1124 FT /evidence="ECO:0000244|PDB:6WEY" FT HELIX 1128..1130 FT /evidence="ECO:0000244|PDB:6WEY" FT HELIX 1131..1136 FT /evidence="ECO:0000244|PDB:6WEY" FT HELIX 1137..1140 FT /evidence="ECO:0000244|PDB:6WEY" FT STRAND 1141..1146 FT /evidence="ECO:0000244|PDB:6WEY" FT HELIX 1152..1154 FT /evidence="ECO:0000244|PDB:6WEN" FT HELIX 1158..1168 FT /evidence="ECO:0000244|PDB:6WEY" FT STRAND 1171..1177 FT /evidence="ECO:0000244|PDB:6WEY" FT HELIX 1180..1191 FT /evidence="ECO:0000244|PDB:6WEY" FT STRAND 1567..1578 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1580..1585 FT /evidence="ECO:0000244|PDB:6WRH" FT HELIX 1590..1594 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1595..1599 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1605..1607 FT /evidence="ECO:0000244|PDB:6W9C" FT HELIX 1611..1613 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1617..1620 FT /evidence="ECO:0000244|PDB:6WRH" FT HELIX 1625..1635 FT /evidence="ECO:0000244|PDB:6WRH" FT HELIX 1642..1653 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1660..1665 FT /evidence="ECO:0000244|PDB:6W9C" FT TURN 1671..1673 FT /evidence="ECO:0000244|PDB:6WX4" FT HELIX 1674..1683 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1690..1692 FT /evidence="ECO:0000244|PDB:6WRH" FT HELIX 1693..1703 FT /evidence="ECO:0000244|PDB:6WRH" FT HELIX 1708..1718 FT /evidence="ECO:0000244|PDB:6WRH" FT HELIX 1728..1737 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1745..1752 FT /evidence="ECO:0000244|PDB:6WRH" FT TURN 1753..1755 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1756..1763 FT /evidence="ECO:0000244|PDB:6WRH" FT HELIX 1765..1768 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1769..1772 FT /evidence="ECO:0000244|PDB:6WRH" FT HELIX 1776..1781 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1783..1786 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1790..1816 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1822..1830 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1833..1849 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1852..1869 FT /evidence="ECO:0000244|PDB:6WRH" FT STRAND 1871..1874 FT /evidence="ECO:0000244|PDB:6WRH" FT HELIX 3274..3277 FT /evidence="ECO:0000244|PDB:6YB7" FT STRAND 3280..3285 FT /evidence="ECO:0000244|PDB:6YB7" FT STRAND 3288..3295 FT /evidence="ECO:0000244|PDB:6YB7" FT STRAND 3298..3302 FT /evidence="ECO:0000244|PDB:6YB7" FT HELIX 3303..3306 FT /evidence="ECO:0000244|PDB:6YB7" FT HELIX 3311..3313 FT /evidence="ECO:0000244|PDB:6YB7" FT HELIX 3317..3322 FT /evidence="ECO:0000244|PDB:6YB7" FT HELIX 3326..3328 FT /evidence="ECO:0000244|PDB:6YB7" FT STRAND 3329..3333 FT /evidence="ECO:0000244|PDB:6YB7" FT STRAND 3336..3338 FT /evidence="ECO:0000244|PDB:6YB7" FT STRAND 3340..3346 FT /evidence="ECO:0000244|PDB:6YB7" FT STRAND 3349..3356 FT /evidence="ECO:0000244|PDB:6YB7" FT STRAND 3363..3366 FT /evidence="ECO:0000244|PDB:6YB7" FT STRAND 3374..3381 FT /evidence="ECO:0000244|PDB:6YB7" FT STRAND 3384..3392 FT /evidence="ECO:0000244|PDB:6YB7" FT STRAND 3411..3416 FT /evidence="ECO:0000244|PDB:6YB7" FT STRAND 3419..3429 FT /evidence="ECO:0000244|PDB:6YB7" FT TURN 3431..3433 FT /evidence="ECO:0000244|PDB:7BRP" FT STRAND 3435..3438 FT /evidence="ECO:0000244|PDB:6YB7" FT STRAND 3444..3447 FT /evidence="ECO:0000244|PDB:7BRR" FT STRAND 3450..3453 FT /evidence="ECO:0000244|PDB:6YB7" FT HELIX 3464..3476 FT /evidence="ECO:0000244|PDB:6YB7" FT HELIX 3490..3499 FT /evidence="ECO:0000244|PDB:6YB7" FT HELIX 3507..3512 FT /evidence="ECO:0000244|PDB:6YB7" FT HELIX 3514..3520 FT /evidence="ECO:0000244|PDB:6YB7" FT HELIX 3524..3537 FT /evidence="ECO:0000244|PDB:6YB7" FT STRAND 3547..3549 FT /evidence="ECO:0000244|PDB:6YB7" FT HELIX 3556..3564 FT /evidence="ECO:0000244|PDB:6YB7" FT HELIX 3565..3568 FT /evidence="ECO:0000244|PDB:7C8T" FT HELIX 3860..3878 FT /evidence="ECO:0000244|PDB:6XIP" FT HELIX 3881..3883 FT /evidence="ECO:0000244|PDB:6XIP" FT HELIX 3885..3899 FT /evidence="ECO:0000244|PDB:6XIP" FT HELIX 3904..3920 FT /evidence="ECO:0000244|PDB:6XIP" FT TURN 3922..3924 FT /evidence="ECO:0000244|PDB:6XIP" FT HELIX 3927..3930 FT /evidence="ECO:0000244|PDB:6WTC" FT HELIX 3952..3970 FT /evidence="ECO:0000244|PDB:6YYT" FT TURN 4011..4013 FT /evidence="ECO:0000244|PDB:7BTF" FT HELIX 4021..4040 FT /evidence="ECO:0000244|PDB:6XIP" FT HELIX 4043..4053 FT /evidence="ECO:0000244|PDB:6XIP" FT STRAND 4058..4060 FT /evidence="ECO:0000244|PDB:6XIP" FT HELIX 4061..4066 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4069..4074 FT /evidence="ECO:0000244|PDB:6XIP" FT HELIX 4077..4083 FT /evidence="ECO:0000244|PDB:6XIP" FT STRAND 4088..4091 FT /evidence="ECO:0000244|PDB:6XIP" FT STRAND 4094..4102 FT /evidence="ECO:0000244|PDB:6XIP" FT HELIX 4111..4113 FT /evidence="ECO:0000244|PDB:6XIP" FT TURN 4116..4118 FT /evidence="ECO:0000244|PDB:6XIP" FT HELIX 4119..4121 FT /evidence="ECO:0000244|PDB:6XIP" FT STRAND 4124..4132 FT /evidence="ECO:0000244|PDB:6XIP" FT STRAND 4144..4148 FT /evidence="ECO:0000244|PDB:6W9Q" FT STRAND 4150..4160 FT /evidence="ECO:0000244|PDB:6WXD" FT STRAND 4165..4175 FT /evidence="ECO:0000244|PDB:6WXD" FT STRAND 4178..4187 FT /evidence="ECO:0000244|PDB:6WXD" FT STRAND 4193..4197 FT /evidence="ECO:0000244|PDB:6WXD" FT STRAND 4199..4202 FT /evidence="ECO:0000244|PDB:6W9Q" FT STRAND 4204..4209 FT /evidence="ECO:0000244|PDB:6WXD" FT STRAND 4213..4219 FT /evidence="ECO:0000244|PDB:6WXD" FT STRAND 4222..4231 FT /evidence="ECO:0000244|PDB:6WXD" FT HELIX 4236..4249 FT /evidence="ECO:0000244|PDB:6WXD" FT HELIX 4264..4273 FT /evidence="ECO:0000244|PDB:6WVN" FT HELIX 4276..4285 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 4307..4311 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 4318..4323 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 4324..4326 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 4328..4332 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 4339..4341 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 4348..4353 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 4354..4356 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 4360..4366 FT /evidence="ECO:0000244|PDB:6W4H" FT TURN 4371..4373 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 4375..4377 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 4397..4404 FT /evidence="ECO:0000244|PDB:7BTF" FT STRAND 4416..4418 FT /evidence="ECO:0000244|PDB:7BTF" FT STRAND 4424..4430 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4435..4441 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4447..4451 FT /evidence="ECO:0000244|PDB:7BTF" FT STRAND 4457..4466 FT /evidence="ECO:0000244|PDB:7BTF" FT HELIX 4477..4481 FT /evidence="ECO:0000244|PDB:7BV2" FT TURN 4482..4484 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4491..4511 FT /evidence="ECO:0000244|PDB:7BTF" FT STRAND 4513..4515 FT /evidence="ECO:0000244|PDB:6M71" FT HELIX 4516..4524 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4528..4530 FT /evidence="ECO:0000244|PDB:7BV1" FT HELIX 4532..4540 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4546..4550 FT /evidence="ECO:0000244|PDB:7BV2" FT TURN 4552..4555 FT /evidence="ECO:0000244|PDB:7BV2" FT TURN 4557..4559 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4563..4567 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4568..4570 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4571..4591 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4593..4596 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4599..4601 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4602..4606 FT /evidence="ECO:0000244|PDB:6YYT" FT STRAND 4623..4625 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4627..4639 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4642..4647 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4649..4651 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4653..4655 FT /evidence="ECO:0000244|PDB:6YYT" FT HELIX 4668..4678 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4690..4692 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4696..4709 FT /evidence="ECO:0000244|PDB:7BV2" FT TURN 4710..4712 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4715..4717 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4718..4727 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4730..4740 FT /evidence="ECO:0000244|PDB:7BV2" FT TURN 4741..4743 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4744..4747 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4753..4756 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4760..4768 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4770..4776 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4777..4784 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4789..4796 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4809..4817 FT /evidence="ECO:0000244|PDB:7BV2" FT TURN 4818..4821 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4840..4845 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4846..4850 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4858..4868 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4869..4872 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4873..4875 FT /evidence="ECO:0000244|PDB:6YYT" FT HELIX 4882..4884 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4890..4893 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4898..4900 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4904..4910 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4913..4922 FT /evidence="ECO:0000244|PDB:7BV2" FT TURN 4923..4925 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4931..4936 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4941..4943 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4948..4951 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4954..4973 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 4976..4979 FT /evidence="ECO:0000244|PDB:7BV2" FT TURN 4986..4988 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 4989..4997 FT /evidence="ECO:0000244|PDB:7BV2" FT TURN 4998..5000 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 5002..5008 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5014..5017 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5020..5030 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5031..5033 FT /evidence="ECO:0000244|PDB:7BV2" FT TURN 5035..5037 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5040..5054 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 5058..5060 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 5062..5067 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 5074..5076 FT /evidence="ECO:0000244|PDB:6YYT" FT HELIX 5079..5100 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5104..5106 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5110..5124 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5131..5144 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 5145..5150 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 5153..5159 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5160..5164 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 5166..5168 FT /evidence="ECO:0000244|PDB:6M71" FT HELIX 5171..5181 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5188..5190 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 5192..5194 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 5197..5199 FT /evidence="ECO:0000244|PDB:6M71" FT STRAND 5204..5206 FT /evidence="ECO:0000244|PDB:6M71" FT STRAND 5207..5214 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 5217..5223 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5226..5234 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 5235..5237 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5239..5242 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5244..5258 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5259..5263 FT /evidence="ECO:0000244|PDB:7BV2" FT STRAND 5264..5266 FT /evidence="ECO:0000244|PDB:6YYT" FT HELIX 5267..5286 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5302..5308 FT /evidence="ECO:0000244|PDB:6YYT" FT HELIX 5310..5314 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 5315..5317 FT /evidence="ECO:0000244|PDB:7BV2" FT HELIX 6454..6464 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6476..6479 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6482..6487 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6490..6496 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6499..6501 FT /evidence="ECO:0000244|PDB:6WLC" FT HELIX 6503..6511 FT /evidence="ECO:0000244|PDB:6WLC" FT HELIX 6521..6526 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6531..6536 FT /evidence="ECO:0000244|PDB:6WLC" FT TURN 6540..6543 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6544..6548 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6550..6553 FT /evidence="ECO:0000244|PDB:6WLC" FT TURN 6555..6557 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6558..6562 FT /evidence="ECO:0000244|PDB:6WLC" FT HELIX 6566..6568 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6569..6571 FT /evidence="ECO:0000244|PDB:6X1B" FT STRAND 6573..6576 FT /evidence="ECO:0000244|PDB:6WLC" FT HELIX 6582..6588 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6590..6598 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6612..6614 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6617..6619 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6622..6624 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6629..6634 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6637..6639 FT /evidence="ECO:0000244|PDB:6X1B" FT HELIX 6660..6667 FT /evidence="ECO:0000244|PDB:6WLC" FT HELIX 6670..6676 FT /evidence="ECO:0000244|PDB:6WLC" FT TURN 6680..6683 FT /evidence="ECO:0000244|PDB:6X4I" FT HELIX 6684..6687 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6693..6696 FT /evidence="ECO:0000244|PDB:6WLC" FT HELIX 6703..6712 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6715..6718 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6726..6734 FT /evidence="ECO:0000244|PDB:6WLC" FT TURN 6735..6737 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6740..6747 FT /evidence="ECO:0000244|PDB:6WLC" FT HELIX 6751..6758 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6765..6774 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6777..6786 FT /evidence="ECO:0000244|PDB:6WLC" FT STRAND 6789..6795 FT /evidence="ECO:0000244|PDB:6WLC" FT HELIX 6800..6803 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 6804..6808 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 6811..6814 FT /evidence="ECO:0000244|PDB:6W4H" FT TURN 6826..6829 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 6840..6852 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 6864..6869 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 6878..6886 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 6892..6899 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 6905..6911 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 6913..6915 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 6916..6920 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 6922..6927 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 6932..6934 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 6947..6958 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 6959..6969 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 6971..6973 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 6976..6982 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 6985..6994 FT /evidence="ECO:0000244|PDB:6W4H" FT TURN 6995..6998 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 7002..7009 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 7019..7032 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 7040..7043 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 7056..7058 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 7062..7064 FT /evidence="ECO:0000244|PDB:6W4H" FT HELIX 7067..7074 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 7078..7081 FT /evidence="ECO:0000244|PDB:6W4H" FT STRAND 7088..7090 FT /evidence="ECO:0000244|PDB:6W4H" SQ SEQUENCE 7096 AA; 794058 MW; A4E62D97150BB8CC 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 NRVCGVSAAR LTPCGTGTST DVVYRAFDIY NDKVAGFAKF LKTNCCRFQE KDEDDNLIDS YFVVKRHTFS NYQHEETIYN LLKDCPAVAK HDFFKFRIDG DMVPHISRQR LTKYTMADLV YALRHFDEGN CDTLKEILVT YNCCDDDYFN KKDWYDFVEN PDILRVYANL GERVRQALLK TVQFCDAMRN AGIVGVLTLD NQDLNGNWYD FGDFIQTTPG SGVPVVDSYY SLLMPILTLT RALTAESHVD TDLTKPYIKW DLLKYDFTEE RLKLFDRYFK YWDQTYHPNC VNCLDDRCIL HCANFNVLFS TVFPPTSFGP LVRKIFVDGV PFVVSTGYHF RELGVVHNQD VNLHSSRLSF KELLVYAADP AMHAASGNLL LDKRTTCFSV AALTNNVAFQ TVKPGNFNKD FYDFAVSKGF FKEGSSVELK HFFFAQDGNA AISDYDYYRY NLPTMCDIRQ LLFVVEVVDK YFDCYDGGCI NANQVIVNNL DKSAGFPFNK WGKARLYYDS MSYEDQDALF AYTKRNVIPT ITQMNLKYAI SAKNRARTVA GVSICSTMTN RQFHQKLLKS IAATRGATVV IGTSKFYGGW HNMLKTVYSD VENPHLMGWD YPKCDRAMPN MLRIMASLVL ARKHTTCCSL SHRFYRLANE CAQVLSEMVM CGGSLYVKPG GTSSGDATTA YANSVFNICQ AVTANVNALL STDGNKIADK YVRNLQHRLY ECLYRNRDVD TDFVNEFYAY LRKHFSMMIL SDDAVVCFNS TYASQGLVAS IKNFKSVLYY QNNVFMSEAK CWTETDLTKG PHEFCSQHTM LVKQGDDYVY LPYPDPSRIL GAGCFVDDIV KTDGTLMIER FVSLAIDAYP LTKHPNQEYA DVFHLYLQYI RKLHDELTGH MLDMYSVMLT NDNTSRYWEP EFYEAMYTPH TVLQAVGACV LCNSQTSLRC GACIRRPFLC CKCCYDHVIS TSHKLVLSVN PYVCNAPGCD VTDVTQLYLG GMSYYCKSHK PPISFPLCAN GQVFGLYKNT CVGSDNVTDF NAIATCDWTN AGDYILANTC TERLKLFAAE TLKATEETFK LSYGIATVRE VLSDRELHLS WEVGKPRPPL NRNYVFTGYR VTKNSKVQIG EYTFEKGDYG DAVVYRGTTT YKLNVGDYFV LTSHTVMPLS APTLVPQEHY VRITGLYPTL NISDEFSSNV ANYQKVGMQK YSTLQGPPGT GKSHFAIGLA LYYPSARIVY TACSHAAVDA LCEKALKYLP IDKCSRIIPA RARVECFDKF KVNSTLEQYV FCTVNALPET TADIVVFDEI SMATNYDLSV VNARLRAKHY VYIGDPAQLP APRTLLTKGT LEPEYFNSVC RLMKTIGPDM FLGTCRRCPA EIVDTVSALV YDNKLKAHKD KSAQCFKMFY KGVITHDVSS AINRPQIGVV REFLTRNPAW RKAVFISPYN SQNAVASKIL GLPTQTVDSS QGSEYDYVIF TQTTETAHSC NVNRFNVAIT RAKVGILCIM SDRDLYDKLQ FTSLEIPRRN VATLQAENVT GLFKDCSKVI TGLHPTQAPT HLSVDTKFKT EGLCVDIPGI PKDMTYRRLI SMMGFKMNYQ VNGYPNMFIT REEAIRHVRA WIGFDVEGCH ATREAVGTNL PLQLGFSTGV NLVAVPTGYV DTPNNTDFSR VSAKPPPGDQ FKHLIPLMYK GLPWNVVRIK IVQMLSDTLK NLSDRVVFVL WAHGFELTSM KYFVKIGPER TCCLCDRRAT CFSTASDTYA CWHHSIGFDY VYNPFMIDVQ QWGFTGNLQS NHDLYCQVHG NAHVASCDAI MTRCLAVHEC FVKRVDWTIE YPIIGDELKI NAACRKVQHM VVKAALLADK FPVLHDIGNP KAIKCVPQAD VEWKFYDAQP CSDKAYKIEE LFYSYATHSD KFTDGVCLFW NCNVDRYPAN SIVCRFDTRV LSNLNLPGCD GGSLYVNKHA FHTPAFDKSA FVNLKQLPFF YYSDSPCESH GKQVVSDIDY VPLKSATCIT RCNLGGAVCR HHANEYRLYL DAYNMMISAG FSLWVYKQFD TYNLWNTFTR LQSLENVAFN VVNKGHFDGQ QGEVPVSIIN NTVYTKVDGV DVELFENKTT LPVNVAFELW AKRNIKPVPE VKILNNLGVD IAANTVIWDY KRDAPAHIST IGVCSMTDIA KKPTETICAP LTVFFDGRVD GQVDLFRNAR NGVLITEGSV KGLQPSVGPK QASLNGVTLI GEAVKTQFNY YKKVDGVVQQ LPETYFTQSR NLQEFKPRSQ MEIDFLELAM DEFIERYKLE GYAFEHIVYG DFSHSQLGGL HLLIGLAKRF KESPFELEDF IPMDSTVKNY FITDAQTGSS KCVCSVIDLL LDDFVEIIKS QDLSVVSKVV KVTIDYTEIS FMLWCKDGHV ETFYPKLQSS QAWQPGVAMP NLYKMQRMLL EKCDLQNYGD SATLPKGIMM NVAKYTQLCQ YLNTLTLAVP YNMRVIHFGA GSDKGVAPGT AVLRQWLPTG TLLVDSDLND FVSDADSTLI GDCATVHTAN KWDLIISDMY DPKTKNVTKE NDSKEGFFTY ICGFIQQKLA LGGSVAIKIT EHSWNADLYK LMGHFAWWTA FVTNVNASSS EAFLIGCNYL GKPREQIDGY VMHANYIFWR NTNPIQLSSY SLFDMSKFPL KLRGTAVMSL KEGQINDMIL SLLSKGRLII RENNRVVISS DVLVNN //