ID A0A679DZB2_9BETC Unreviewed; 7093 AA. AC A0A679DZB2; DT 17-JUN-2020, integrated into UniProtKB/TrEMBL. DT 17-JUN-2020, sequence version 1. DT 24-JAN-2024, entry version 18. DE RecName: Full=ORF1ab polyprotein {ECO:0000256|PROSITE-ProRule:PRU01344}; OS Bovine coronavirus. OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes; OC Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae; OC Betacoronavirus; Embecovirus; Betacoronavirus 1. OX NCBI_TaxID=11128 {ECO:0000313|EMBL:BBM61534.1}; RN [1] {ECO:0000313|EMBL:BBM61534.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=TCG-29 {ECO:0000313|EMBL:BBM61534.1}; RA Suzuki T., Otake Y., Uchimoto S., Hasebe A., Goto Y.; RT "Genomic characterization and phylogenetic classification of bovine RT coronaviruses through whole genome sequence analysis."; RL Viruses 12:0-183(2020). CC -!- FUNCTION: Catalytic subunit of viral RNA capping enzyme which catalyzes CC the RNA guanylyltransferase reaction for genomic and sub-genomic RNAs. CC The kinase-like NiRAN domain of NSP12 transfers RNA to the amino CC terminus of NSP9, forming a covalent RNA-protein intermediate. CC Subsequently, the NiRAN domain transfers RNA to GDP, forming the core CC cap structure GpppA-RNA. The NSP14 and NSP16 methyltransferases then CC add methyl groups to form functional cap structures. CC {ECO:0000256|ARBA:ARBA00034461}. CC -!- FUNCTION: Cleaves the C-terminus of replicase polyprotein at 11 sites. CC Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. CC Also able to bind an ADP-ribose-1''-phosphate (ADRP). CC {ECO:0000256|ARBA:ARBA00002223}. CC -!- FUNCTION: Forms a hexadecamer with nsp7 (8 subunits of each) that may CC participate in viral replication by acting as a primase. Alternatively, CC may synthesize substantially longer products than oligonucleotide CC primers. {ECO:0000256|ARBA:ARBA00002182}. CC -!- FUNCTION: Forms a hexadecamer with nsp8 (8 subunits of each) that may CC participate in viral replication by acting as a primase. Alternatively, CC may synthesize substantially longer products than oligonucleotide CC primers. {ECO:0000256|ARBA:ARBA00003443}. CC -!- FUNCTION: Inhibits host translation by interacting with the 40S CC ribosomal subunit. The nsp1-40S ribosome complex further induces an CC endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them CC for degradation. Viral mRNAs are not susceptible to nsp1-mediated CC endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader CC sequence and are therefore protected from degradation. By suppressing CC host gene expression, nsp1 facilitates efficient viral gene expression CC in infected cells and evasion from host immune response. CC {ECO:0000256|ARBA:ARBA00002872}. CC -!- FUNCTION: May play a role in the modulation of host cell survival CC signaling pathway by interacting with host PHB and PHB2. Indeed, these CC two proteins play a role in maintaining the functional integrity of the CC mitochondria and protecting cells from various stresses. CC {ECO:0000256|ARBA:ARBA00003115}. CC -!- FUNCTION: Methyltransferase that mediates mRNA cap 2'-O-ribose CC methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine CC cap is a prerequisite for binding of nsp16. Therefore plays an CC essential role in viral mRNAs cap methylation which is essential to CC evade immune system. {ECO:0000256|ARBA:ARBA00002840}. CC -!- FUNCTION: Multi-functional protein with a zinc-binding domain in N- CC terminus displaying RNA and DNA duplex-unwinding activities with 5' to CC 3' polarity. Activity of helicase is dependent on magnesium. CC {ECO:0000256|ARBA:ARBA00002960}. CC -!- FUNCTION: Participates in the assembly of virally-induced cytoplasmic CC double-membrane vesicles necessary for viral replication. CC {ECO:0000256|ARBA:ARBA00003070}. CC -!- FUNCTION: Plays a pivotal role in viral transcription by stimulating CC both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase CC activities. Therefore plays an essential role in viral mRNAs cap CC methylation. {ECO:0000256|ARBA:ARBA00002697}. CC -!- FUNCTION: Plays a role in the initial induction of autophagosomes from CC host reticulum endoplasmic. Later, limits the expansion of these CC phagosomes that are no longer able to deliver viral components to CC lysosomes. {ECO:0000256|ARBA:ARBA00003748}. CC -!- FUNCTION: Plays a role in viral RNA synthesis through two distinct CC activities. The N7-guanine methyltransferase activity plays a role in CC the formation of the cap structure GpppA-RNA. The proofreading CC exoribonuclease reduces the sensitivity of the virus to RNA mutagens CC during replication. This activity acts on both ssRNA and dsRNA in a 3'- CC 5' direction. {ECO:0000256|ARBA:ARBA00034456}. CC -!- FUNCTION: Plays a role in viral transcription/replication and prevents CC the simultaneous activation of host cell dsRNA sensors, such as CC MDA5/IFIH1, OAS, and PKR (By similarity). Acts by degrading the 5'- CC polyuridines generated during replication of the poly(A) region of CC viral genomic and subgenomic RNAs. Catalyzes a two-step reaction in CC which a 2'3'-cyclic phosphate (2'3'-cP) is first generated by 2'-O CC transesterification, which is then hydrolyzed to a 3'-phosphate (3'-P) CC (By similarity). If not degraded, poly(U) RNA would hybridize with CC poly(A) RNA tails and activate host dsRNA sensors. CC {ECO:0000256|ARBA:ARBA00025521}. CC -!- FUNCTION: RNA-directed RNA polymerase that catalyzes the transcription CC of viral genomic and subgenomic RNAs. Acts in complex with nsp7 and CC nsp8 to transcribe both the minus and positive strands of genomic RNA. CC Subgenomic RNAs (sgRNAs) are formed by discontinuous transcription: The CC polymerase has the ability to pause at transcription-regulating CC sequences (TRS) and jump to the leader TRS, resulting in a major CC deletion. This creates a series of subgenomic RNAs that are replicated, CC transcribed and translated. In addition, Nsp12 is a subunit of the CC viral RNA capping enzyme that catalyzes the RNA guanylyltransferase CC reaction for genomic and sub-genomic RNAs. The kinase-like NiRAN domain CC of NSP12 transfers RNA to the amino terminus of NSP9, forming a CC covalent RNA-protein intermediate. Subsequently, the NiRAN domain CC transfers RNA to GDP, and forms the core cap structure GpppA-RNA. CC {ECO:0000256|ARBA:ARBA00034462}. CC -!- FUNCTION: Responsible for the cleavages located at the N-terminus of CC the replicase polyprotein. 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 Participates together with nsp4 in the assembly of virally-induced CC cytoplasmic double-membrane vesicles necessary for viral replication. CC Antagonizes innate immune induction of type I interferon by blocking CC the phosphorylation, dimerization and subsequent nuclear translocation CC of host IRF3. Prevents also host NF-kappa-B signaling. CC {ECO:0000256|ARBA:ARBA00003569}. CC -!- FUNCTION: The replicase polyprotein of coronaviruses is a CC multifunctional protein: it contains the activities necessary for the CC transcription of negative stranded RNA, leader RNA, subgenomic mRNAs CC and progeny virion RNA as well as proteinases responsible for the CC cleavage of the polyprotein into functional products. CC {ECO:0000256|ARBA:ARBA00003368}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; CC Evidence={ECO:0000256|ARBA:ARBA00001665}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; CC Evidence={ECO:0000256|ARBA:ARBA00001556}; CC -!- CATALYTIC ACTIVITY: 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:0000256|ARBA:ARBA00000707}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA + CC S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'- CC triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L- CC homocysteine; Xref=Rhea:RHEA:67008, Rhea:RHEA-COMP:17166, Rhea:RHEA- CC COMP:17167, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, CC ChEBI:CHEBI:167617; EC=2.1.1.56; CC Evidence={ECO:0000256|ARBA:ARBA00034403}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67009; CC Evidence={ECO:0000256|ARBA:ARBA00034403}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside CC in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'- CC triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S- CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:67020, Rhea:RHEA-COMP:17167, CC Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, ChEBI:CHEBI:167609; CC EC=2.1.1.57; Evidence={ECO:0000256|ARBA:ARBA00024256}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end diphospho-ribonucleoside in mRNA + GTP + H(+) = a 5'- CC end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA + diphosphate; CC Xref=Rhea:RHEA:67012, Rhea:RHEA-COMP:17165, Rhea:RHEA-COMP:17166, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:167616, ChEBI:CHEBI:167617; EC=2.7.7.50; CC Evidence={ECO:0000256|ARBA:ARBA00024520}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67013; CC Evidence={ECO:0000256|ARBA:ARBA00024520}; CC -!- CATALYTIC ACTIVITY: CC Reaction=uridylyl-uridylyl-ribonucleotide-RNA = a 3'-end uridylyl- CC 2',3'-cyclophospho-uridine-RNA + a 5'-end dephospho-ribonucleoside- CC RNA; Xref=Rhea:RHEA:67732, Rhea:RHEA-COMP:13936, Rhea:RHEA- CC COMP:17334, Rhea:RHEA-COMP:17335, ChEBI:CHEBI:138284, CC ChEBI:CHEBI:173079, ChEBI:CHEBI:173080; CC Evidence={ECO:0000256|ARBA:ARBA00024600}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000256|ARBA:ARBA00001946}; CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000256|ARBA:ARBA00001936}; CC -!- SUBUNIT: Interacts with host PHB and PHB2. CC {ECO:0000256|ARBA:ARBA00025984}. CC -!- SUBUNIT: Interacts with nsp12. {ECO:0000256|ARBA:ARBA00034503}. CC -!- SUBUNIT: Interacts with nsp7 and nsp8 to form the replication- CC transcription complex (RTC): nsp12, nsp7, two subunits of nsp8, and up CC to two subunits of nsp13. Interacts with nsp9. CC {ECO:0000256|ARBA:ARBA00034511}. CC -!- SUBUNIT: Interacts with nsp7, nsp13 and nsp12 to form the replication- CC transcription complex (RTC): nsp12, nsp7, two subunits of nsp8, and up CC to two subunits of nsp13. {ECO:0000256|ARBA:ARBA00034514}. CC -!- SUBUNIT: Interacts with nsp8 and nsp12 to form the replication- CC transcription complex (RTC): nsp12, nsp7, two subunits of nsp8, and up CC to two subunits of nsp13. {ECO:0000256|ARBA:ARBA00034507}. CC -!- SUBUNIT: Interacts with nsp8 to form the replication-transcription CC complex (RTC): nsp12, nsp7, two subunits of nsp8, and up to two CC subunits of nsp13. {ECO:0000256|ARBA:ARBA00034500}. CC -!- SUBUNIT: Interacts with papain-like protease nsp3 and non-structural CC protein 6. {ECO:0000256|ARBA:ARBA00034512}. CC -!- SUBUNIT: Interacts with proofreading exoribonuclease nsp14 and 2'-O- CC methyltransferase nsp16; these interactions enhance nsp14 and nsp16 CC enzymatic activities. {ECO:0000256|ARBA:ARBA00034506}. CC -!- SUBUNIT: Monomer. Homodimer. Only the homodimer shows catalytic CC activity. {ECO:0000256|ARBA:ARBA00034508}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum-Golgi intermediate CC compartment {ECO:0000256|ARBA:ARBA00004399}. Host cytoplasm, host CC perinuclear region {ECO:0000256|ARBA:ARBA00004407}. Host endoplasmic CC reticulum-Golgi intermediate compartment CC {ECO:0000256|ARBA:ARBA00004452}. Host membrane CC {ECO:0000256|ARBA:ARBA00004301}; Multi-pass membrane protein CC {ECO:0000256|ARBA:ARBA00004301}. Membrane CC {ECO:0000256|ARBA:ARBA00004141}; Multi-pass membrane protein CC {ECO:0000256|ARBA:ARBA00004141}. CC -!- SIMILARITY: Belongs to the coronaviruses polyprotein 1ab family. CC {ECO:0000256|ARBA:ARBA00008087, ECO:0000256|PROSITE-ProRule:PRU01294}. 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; LC494188; BBM61534.1; -; Genomic_RNA. DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IEA:UniProtKB-SubCell. 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:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0000175; F:3'-5'-RNA exonuclease activity; IEA:InterPro. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:UniProtKB-EC. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro. DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-UniRule. DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW. DR GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; IEA:InterPro. DR GO; GO:0004482; F:mRNA 5'-cap (guanine-N7-)-methyltransferase activity; IEA:InterPro. DR GO; GO:0008242; F:omega peptidase activity; IEA:InterPro. DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC. DR GO; GO:0003968; F:RNA-dependent RNA polymerase activity; IEA:UniProtKB-KW. DR GO; GO:0003727; F:single-stranded RNA binding; IEA:InterPro. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro. DR GO; GO:0039595; P:induction by virus of catabolism of host mRNA; IEA:UniProtKB-UniRule. DR GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW. DR GO; GO:0039648; P:modulation by symbiont of host protein ubiquitination; IEA:UniProtKB-KW. 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; IEA:UniProtKB-KW. DR GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; IEA:UniProtKB-KW. DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-UniRule. DR GO; GO:0019082; P:viral protein processing; IEA:InterPro. DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro. DR CDD; cd21409; 1B_cv_Nsp13-like; 1. DR CDD; cd21901; alpha_betaCoV_Nsp10; 1. DR CDD; cd21560; betaCoV-Nsp6; 1. DR CDD; cd21722; betaCoV_Nsp13-helicase; 1. DR CDD; cd21659; betaCoV_Nsp14; 1. DR CDD; cd21519; betaCoV_Nsp2_MHV-like; 1. DR CDD; cd21666; betaCoV_Nsp5_Mpro; 1. DR CDD; cd21827; betaCoV_Nsp7; 1. DR CDD; cd21831; betaCoV_Nsp8; 1. DR CDD; cd21898; betaCoV_Nsp9; 1. DR CDD; cd21732; betaCoV_PLPro; 1. DR CDD; cd20762; capping_2-OMTase_Nidovirales; 1. DR CDD; cd21473; cv_Nsp4_TM; 1. DR CDD; cd21524; DPUP_MHV_Nsp3; 1. DR CDD; cd21593; HCoV_HKU1-like_RdRp; 1. DR CDD; cd21167; M_alpha_beta_cv_Nsp15-like; 1. DR CDD; cd21557; Macro_X_Nsp3-like; 1. DR CDD; cd21879; MHV-like_Nsp1; 1. DR CDD; cd21812; MHV-like_Nsp3_betaSM; 1. DR CDD; cd21824; MHV-like_Nsp3_NAB; 1. DR CDD; cd21161; NendoU_cv_Nsp15-like; 1. DR CDD; cd21171; NTD_alpha_betaCoV_Nsp15-like; 1. DR CDD; cd21689; stalk_CoV_Nsp13-like; 1. DR CDD; cd21714; TM_Y_MHV-like_Nsp3_C; 1. DR CDD; cd21467; Ubl1_cv_Nsp3_N-like; 1. DR CDD; cd21401; ZBD_cv_Nsp13-like; 1. DR Gene3D; 1.10.8.1190; -; 2. DR Gene3D; 2.60.120.1680; -; 1. DR Gene3D; 3.10.20.350; -; 1. DR Gene3D; 3.10.20.540; -; 1. DR Gene3D; 3.40.50.11580; -; 1. DR Gene3D; 6.10.140.2090; -; 1. DR Gene3D; 1.10.150.420; Coronavirus nonstructural protein 4 C-terminus; 1. DR Gene3D; 3.40.220.10; Leucine Aminopeptidase, subunit E, domain 1; 1. DR Gene3D; 1.10.1840.10; main proteinase (3clpro) structure, domain 3; 1. DR Gene3D; 3.30.160.820; Nsp15 N-terminal domain-like; 1. DR Gene3D; 1.10.8.370; nsp7 replicase; 1. DR Gene3D; 3.30.70.3540; Nsp8 replicase, head domain; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR Gene3D; 2.40.10.250; Replicase NSP9; 1. DR Gene3D; 3.40.50.11020; Replicase polyprotein, nucleic acid-binding domain; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR InterPro; IPR027351; (+)RNA_virus_helicase_core_dom. DR InterPro; IPR046443; a/bCoV_NSP1_glob. DR InterPro; IPR046440; AV_NSP11N_COV_NSP15M. DR InterPro; IPR022570; B-CoV_A_NSP1. DR InterPro; IPR046442; bCoV_NSP1_C. DR InterPro; IPR043608; CoV_NSP15_M. DR InterPro; IPR043606; CoV_NSP15_N. DR InterPro; IPR043613; CoV_NSP2_C. DR InterPro; IPR047573; CoV_NSP2_M. DR InterPro; IPR043611; CoV_NSP3_C. DR InterPro; IPR047566; CoV_NSP3_Y3. DR InterPro; IPR032505; CoV_NSP4_C. DR InterPro; IPR043612; CoV_NSP4_N. DR InterPro; 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; IPR044371; Macro_X_NSP3-like. DR InterPro; IPR046435; N7_MTase_CoV. DR InterPro; IPR043609; NendoU_nidovirus. DR InterPro; IPR044863; NIRAN. DR InterPro; IPR046438; NIV_2_O_MTASE. DR InterPro; IPR046436; NIV_EXON. DR InterPro; IPR036333; NSP10_sf_CoV. DR InterPro; IPR047570; NSP12_IF_CoV. DR InterPro; IPR044343; NSP13_1B_dom_CoV. DR InterPro; IPR048673; NSP13_stalk_CoV. DR InterPro; IPR048672; NSP13_ZBD_CoV. DR InterPro; IPR027352; NSP13_ZBD_CoV-like. DR InterPro; IPR044315; NSP14_betaCoV. DR InterPro; IPR009466; NSP14_CoV. DR InterPro; IPR044330; NSP15_alpha_betaCoV_N. DR InterPro; IPR044322; NSP15_M_alpha_beta_CoV. DR InterPro; IPR043174; NSP15_middle_sf. DR InterPro; IPR042515; NSP15_N_CoV. DR InterPro; IPR044401; NSP15_NendoU_CoV. DR InterPro; IPR009461; NSP16_CoV-like. DR InterPro; IPR044384; NSP2_MHV-like. DR InterPro; IPR043615; NSP2_N_CoV. DR InterPro; IPR044381; NSP3_DPUP_MHV. DR InterPro; IPR047567; NSP3_G2M_bCoV. DR InterPro; IPR032592; NSP3_NAB_bCoV. DR InterPro; IPR042570; NSP3_NAB_bCoV_sf. 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; IPR027417; P-loop_NTPase. DR InterPro; IPR002705; Pept_C30/C16_B_coronavir. 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; IPR046441; RdRp_CoV. DR InterPro; IPR044347; RdRp_HCoV_HKU1-like. DR InterPro; IPR009469; RdRp_N_CoV. DR InterPro; IPR001205; RNA-dir_pol_C. DR InterPro; IPR007094; RNA-dir_pol_PSvirus. DR InterPro; IPR018995; RNA_synth_NSP10_CoV. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR PANTHER; PTHR43788:SF16; AAA_12 DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR43788; DNA2/NAM7 HELICASE FAMILY MEMBER; 1. DR Pfam; PF13087; AAA_12; 1. DR Pfam; PF13604; AAA_30; 1. DR Pfam; PF11963; B-CoV_A_NSP1; 1. DR Pfam; PF16251; bCoV_NAB; 1. DR Pfam; PF06471; CoV_ExoN; 1. DR Pfam; PF06460; CoV_Methyltr_2; 1. DR Pfam; PF09401; CoV_NSP10; 1. DR Pfam; PF20631; CoV_NSP13_1B; 1. DR Pfam; PF20633; CoV_NSP13_stalk; 1. DR Pfam; PF20632; CoV_NSP13_ZBD; 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; 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; PF01831; Peptidase_C16; 1. DR Pfam; PF05409; Peptidase_C30; 1. DR Pfam; PF00680; RdRP_1; 1. DR SMART; SM00506; A1pp; 1. DR SUPFAM; SSF144246; Coronavirus NSP10-like; 1. DR SUPFAM; SSF140367; Coronavirus NSP7-like; 1. DR SUPFAM; SSF143076; Coronavirus NSP8-like; 1. DR SUPFAM; SSF56672; DNA/RNA polymerases; 1. DR SUPFAM; SSF142877; EndoU-like; 1. DR SUPFAM; SSF52949; Macro domain-like; 1. DR SUPFAM; SSF159936; NSP3A-like; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF101816; Replicase NSP9; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS51961; AV_NSP11N_COV_NSP15M; 1. DR PROSITE; PS51963; BCOV_NSP1_C; 1. DR PROSITE; PS51942; BCOV_NSP3C_C; 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; PS51954; COV_N7_MTASE; 1. DR PROSITE; PS51962; COV_NSP1; 1. DR PROSITE; PS52000; COV_NSP12_IF; 1. DR PROSITE; PS51948; COV_NSP12_RDRP; 1. DR PROSITE; PS51960; COV_NSP15_NTD; 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; PS51653; CV_ZBD; 1. DR PROSITE; PS51442; M_PRO; 1. DR PROSITE; PS51154; MACRO; 1. DR PROSITE; PS51958; NENDOU; 1. DR PROSITE; PS51947; NIRAN; 1. DR PROSITE; PS51955; NIV_2_O_MTASE; 1. DR PROSITE; PS51953; NIV_EXON; 1. DR PROSITE; PS51124; PEPTIDASE_C16; 2. DR PROSITE; PS51657; PSRV_HELICASE; 1. DR PROSITE; PS50507; RDRP_SSRNA_POS; 1. PE 3: Inferred from homology; KW Activation of host autophagy by virus {ECO:0000256|ARBA:ARBA00023050}; KW ATP-binding {ECO:0000256|ARBA:ARBA00022840}; KW Decay of host mRNAs by virus {ECO:0000256|ARBA:ARBA00022616}; KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157}; KW Endonuclease {ECO:0000256|ARBA:ARBA00022759, ECO:0000256|PROSITE- KW ProRule:PRU01303}; KW Eukaryotic host gene expression shutoff by virus KW {ECO:0000256|ARBA:ARBA00023247}; KW Eukaryotic host translation shutoff by virus KW {ECO:0000256|ARBA:ARBA00022809, ECO:0000256|PROSITE-ProRule:PRU01308}; KW Exonuclease {ECO:0000256|ARBA:ARBA00022839, ECO:0000256|PROSITE- KW ProRule:PRU01298}; Helicase {ECO:0000256|ARBA:ARBA00022806}; KW Host cytoplasm {ECO:0000256|ARBA:ARBA00023200}; KW Host gene expression shutoff by virus {ECO:0000256|ARBA:ARBA00022995}; KW Host membrane {ECO:0000256|ARBA:ARBA00022870}; KW Host mRNA suppression by virus {ECO:0000256|ARBA:ARBA00022557, KW ECO:0000256|PROSITE-ProRule:PRU01308}; KW Host-virus interaction {ECO:0000256|ARBA:ARBA00022581}; KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|PROSITE- KW ProRule:PRU01303}; KW Inhibition of host innate immune response by virus KW {ECO:0000256|ARBA:ARBA00022632, ECO:0000256|PROSITE-ProRule:PRU01308}; KW Inhibition of host interferon signaling pathway by virus KW {ECO:0000256|ARBA:ARBA00022830, ECO:0000256|PROSITE-ProRule:PRU01308}; KW Inhibition of host ISG15 by virus {ECO:0000256|ARBA:ARBA00023208}; KW Inhibition of host NF-kappa-B by virus {ECO:0000256|ARBA:ARBA00022863}; KW Lyase {ECO:0000256|ARBA:ARBA00023239}; KW Manganese {ECO:0000256|ARBA:ARBA00023211}; KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|SAM:Phobius}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723}; KW Methyltransferase {ECO:0000256|ARBA:ARBA00022603, ECO:0000256|PROSITE- KW ProRule:PRU01299}; KW Modulation of host ubiquitin pathway by viral deubiquitinase KW {ECO:0000256|ARBA:ARBA00022876}; KW Modulation of host ubiquitin pathway by virus KW {ECO:0000256|ARBA:ARBA00022662}; KW Nuclease {ECO:0000256|ARBA:ARBA00022722, ECO:0000256|PROSITE- KW ProRule:PRU01298}; Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741}; KW Nucleotidyltransferase {ECO:0000256|ARBA:ARBA00022695}; KW Protease {ECO:0000256|ARBA:ARBA00022670}; KW Repeat {ECO:0000256|ARBA:ARBA00022737}; KW Ribosomal frameshifting {ECO:0000256|ARBA:ARBA00022758}; KW RNA-binding {ECO:0000256|ARBA:ARBA00022884, ECO:0000256|PROSITE- KW ProRule:PRU01289}; KW RNA-directed RNA polymerase {ECO:0000256|ARBA:ARBA00022484}; KW Thiol protease {ECO:0000256|ARBA:ARBA00022807}; KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PROSITE- KW ProRule:PRU01299}; KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, ECO:0000256|SAM:Phobius}; KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989, KW ECO:0000256|SAM:Phobius}; KW Ubl conjugation pathway {ECO:0000256|ARBA:ARBA00022786}; KW Viral immunoevasion {ECO:0000256|ARBA:ARBA00023280, ECO:0000256|PROSITE- KW ProRule:PRU01308}; Viral RNA replication {ECO:0000256|ARBA:ARBA00022953}; KW Zinc {ECO:0000256|ARBA:ARBA00022833}; KW Zinc-finger {ECO:0000256|ARBA:ARBA00022771, ECO:0000256|PROSITE- KW ProRule:PRU00444}. FT TRANSMEM 2133..2155 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 2193..2218 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 2316..2335 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 2355..2378 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 2754..2777 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 3025..3050 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 3062..3083 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 3123..3144 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 3554..3577 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 3589..3607 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 3614..3635 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 3655..3676 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 3683..3703 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 3754..3773 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT DOMAIN 54..196 FT /note="CoV Nsp1 globular" FT /evidence="ECO:0000259|PROSITE:PS51962" FT DOMAIN 216..246 FT /note="BetaCoV Nsp1 C-terminal" FT /evidence="ECO:0000259|PROSITE:PS51963" FT DOMAIN 250..519 FT /note="CoV Nsp2 N-terminal" FT /evidence="ECO:0000259|PROSITE:PS51989" FT DOMAIN 524..713 FT /note="CoV Nsp2 middle" FT /evidence="ECO:0000259|PROSITE:PS51990" FT DOMAIN 733..851 FT /note="CoV Nsp2 C-terminal" FT /evidence="ECO:0000259|PROSITE:PS51991" FT DOMAIN 853..966 FT /note="Ubiquitin-like" FT /evidence="ECO:0000259|PROSITE:PS51943" FT DOMAIN 1036..1286 FT /note="Peptidase C16" FT /evidence="ECO:0000259|PROSITE:PS51124" FT DOMAIN 1264..1435 FT /note="Macro" FT /evidence="ECO:0000259|PROSITE:PS51154" FT DOMAIN 1490..1562 FT /note="DPUP" FT /evidence="ECO:0000259|PROSITE:PS51942" FT DOMAIN 1561..1616 FT /note="Ubiquitin-like" FT /evidence="ECO:0000259|PROSITE:PS51944" FT DOMAIN 1630..1891 FT /note="Peptidase C16" FT /evidence="ECO:0000259|PROSITE:PS51124" FT DOMAIN 1905..2006 FT /note="Nucleic acid-binding" FT /evidence="ECO:0000259|PROSITE:PS51945" FT DOMAIN 2019..2168 FT /note="G2M" FT /evidence="ECO:0000259|PROSITE:PS51994" FT DOMAIN 2646..2749 FT /note="CoV Nsp3 Y" FT /evidence="ECO:0000259|PROSITE:PS51992" FT DOMAIN 3148..3245 FT /note="Nsp4C" FT /evidence="ECO:0000259|PROSITE:PS51946" FT DOMAIN 3246..3548 FT /note="Peptidase C30" FT /evidence="ECO:0000259|PROSITE:PS51442" FT DOMAIN 3836..3924 FT /note="RdRp Nsp7 cofactor" FT /evidence="ECO:0000259|PROSITE:PS51949" FT DOMAIN 3925..4121 FT /note="RdRp Nsp8 cofactor" FT /evidence="ECO:0000259|PROSITE:PS51950" FT DOMAIN 4122..4231 FT /note="Nsp9 ssRNA-binding" FT /evidence="ECO:0000259|PROSITE:PS51951" FT DOMAIN 4232..4369 FT /note="ExoN/MTase coactivator" FT /evidence="ECO:0000259|PROSITE:PS51952" FT DOMAIN 4374..4629 FT /note="NiRAN" FT /evidence="ECO:0000259|PROSITE:PS51947" FT DOMAIN 4630..4728 FT /note="Nsp12 Interface" FT /evidence="ECO:0000259|PROSITE:PS52000" FT DOMAIN 4729..5296 FT /note="Nsp12 RNA-dependent RNA polymerase" FT /evidence="ECO:0000259|PROSITE:PS51948" FT DOMAIN 4976..5138 FT /note="RdRp catalytic" FT /evidence="ECO:0000259|PROSITE:PS50507" FT DOMAIN 5297..5380 FT /note="CV ZBD" FT /evidence="ECO:0000259|PROSITE:PS51653" FT DOMAIN 5552..5903 FT /note="(+)RNA virus helicase C-terminal" FT /evidence="ECO:0000259|PROSITE:PS51657" FT DOMAIN 5970..6185 FT /note="ExoN" FT /evidence="ECO:0000259|PROSITE:PS51953" FT DOMAIN 6194..6420 FT /note="N7-MTase" FT /evidence="ECO:0000259|PROSITE:PS51954" FT DOMAIN 6421..6481 FT /note="Nsp15 N-terminal oligomerization" FT /evidence="ECO:0000259|PROSITE:PS51960" FT DOMAIN 6482..6602 FT /note="AV-Nsp11N/CoV-Nsp15M" FT /evidence="ECO:0000259|PROSITE:PS51961" FT DOMAIN 6652..6791 FT /note="NendoU" FT /evidence="ECO:0000259|PROSITE:PS51958" FT DOMAIN 6796..7090 FT /note="Nidovirus-type SAM-dependent 2'-O-MTase" FT /evidence="ECO:0000259|PROSITE:PS51955" FT REGION 6307..6321 FT /note="GpppA-binding" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01299" FT ACT_SITE 5988 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01298" FT ACT_SITE 5990 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01298" FT ACT_SITE 6089 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01298" FT ACT_SITE 6166 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01298" FT ACT_SITE 6171 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01298" FT ACT_SITE 6682 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01303" FT ACT_SITE 6697 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01303" FT ACT_SITE 6737 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01303" FT BINDING 6229..6235 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01299" SQ SEQUENCE 7093 AA; 797047 MW; B4BD8CAD7AC6620B CRC64; MSKINKYGLE LHWAPEFPWM FEDAEEKLDN PSSSEVDIFC STTAQKLETG GICPENHVMV DCRRLLKQEC CVQSSLIREI VMNTRPYDLE VLLQDALQSR EAVLVTPPLG MSLEACYVRG CNPKGWTMGL FRRRSVCNTG RCAVNKHVAY QLYMIDPAGV CFGAGQFVGW VIPLAFMPVQ SRKFIVPWVM YLRKCGEKGA YNKDHKRGGF EHVYNFKVED AYDLVHDEPK GKFSKKAYAL IRGYRGVKPL LYVDQYGCDY TGGLADGLEA YADKTLQEMK ALFPIWSQEL HFDVIVAWHV VRDPRYVMRL QSASTIRSVA YVANPTEDLC DGSVVIKEPV HVYADDSIIL RQHNLVDIMS CFYMEADAVV NAFYGVDLKN CGFVMQFGYI DCEQDSCDFK GWVPGNMIDG FACTTCGHVY ETGDLLAQSS GVLPVNPVLH TKSAAGYGGF GCKDSFTLYG QTVVYFGGCV YWSPARNIWI PILKSSVKSY DGLVYTGVVG CKAIVKETNL ICKALYLDYV QHKCGNLHQR ELLGVSDVWH KQLLLNRGVY KPLLENIDYF NMQRAKFSLE TFTVCADGFM PFLLDDLVPR AYYLAVSGQA FCDYADKICH AVVSKSKELL DVSLDSLSAA IHYLNSKIVD LAQHFSGFGT SFVSKIVHFF KTFTTGTALA FAWVLFHVLH GAYIVVESDI YFVKNIPRYA SAVAQAFRSV AKVVLDSLRV TFIDGLSCFK IGRRRICLSG SKIYEVERGL LHSSQLPLDV YDLTMPSQVQ KAKQKPIYLK GSGSDFSLAD SVVEVVTTSL TPCGYSEPPK VADKICIVDN VYMAKAGDKY YPVVVDGHVG LLDQAWRVPC AGRRVTFKEQ PTVNEIASTP KTIKVFYELD KDFNTILNTA CGVFEVDDTV DMEEFYAVVV DAIEEKLSPC KELEGVGAKV SAFLQKLEDN SLFLFDEAGE EVLASKLYCA FTAPEDDDFL EESVVEEDDV EGEETDLTVT SAGEPCVASE QEESSEILED TLDDGPCVET SDSQVEEDVE MSDFADLESV IQDYENVCFE FYTTEPEFVK VLDLYVPKAT RNNCWLRSVL AVMQKLPCQF KDKNLQDLWV LYKQQYSQLF VDTLVNKIPA NIVVPQGGYV ADFAYWFLTL CDWQCVAYWK CIKCDLALKL KGLDAMFFYG DVVSHVCKCG ESMVLIDVDV PFTAHFALKD KLFCAFITKR SVYKAACVVD VNDSHSMAVV DGKQIDDRRV TSITSDKFDF IIGHGMSFSM TTFEIAQLYG SCITPNVCFV KGDIIKVSKC VKAEVVVNPA NGNMAHGGGV AKAIAVAAGQ QFVKETTDMV KSKGVCATGD CYVSTGGKLC KTVLNVVGPD ARTQGKQSYA LLERVYKHLN KYDCVVTTLI SAGIFSVPSD VSLTYLLGTA EKQVVLVSNN QEDFDLISKC QITAVEGTKK LAERLSFNVG RSIVYETDAN KLISNDVAFV STFNVLQDVL SLRHDIALDD DARTFVQSNV DVVPEGWRVV NKFCQINGVR TVKYFECPGG IDICSQDKVF GYVQQGSFNK ATVAQIKALF LDKVDILLTV DGVNFTNRFV PVGESFGKSL GNVFCDGVNV TKHKCDINYK GKVFFQFDNL SSEDLKAVRS SFNFDQKELL AYYNMLVNCS KWQVVFNGKY FTFKQANNNC FVNVSCLMLQ SLNLKFKIVQ WQEAWLEFRS GRPARFVSLV LAKGGFKFGD PADSRDFLRV VFSQVDLTGA ICDFEIACKC GVKQEQRTGV DAVMHFGTLS REDLEIGYTV DCSCGRKLIH CVRFDIPFLI CSNTPSSVKL PKGVGSANIF KGDKVGHYVH VKCEQSYQLY DASNVKKVTD VTGNLSDCLY LKNLKQTFKS VLTTYYLDDV KKIEYKPDLS QYYCDGGKYY TQRIIKAQFK TFEKVDGVYT NFKLIGHTIC DILNAKLGFD SSKEFVEYKV TEWPTATGDV VLATDDLYVK RYERGCITFG KPVIWLSHEQ ASLNSLTYFN RPLLVDENKF DVLKVDDVDD GGDILDSDAK ESKEINIIKL SGVKKPFKVE DSVIVNDDTS EIKYVKSLSI VDVYDMWLTG CRYVVRTANA LSMAVNVPTI RKFIKFGMTL VSIPIDLLNL TEIKPVFNVV KALRNKISAC FNFIKWLFVL LFGWIKTSAD NKVIYTTEVA SKLTCKLVAL AFKNAFLTFN WSVVARGACI IATIFLLWFN FIYANVIFSD FYLPKIGFLP TFVGKIAQWI KSTFSLVTIC DLYSIQDVGF KNQYCNGSIA CQFCLAGFDM LDNYKAIDVV QYEADRRAFV DYTGVLKIVI ELIVSYALYT AWFYPLFALI SIQILTTWLP ELFMLSTLHW SVRLLVSLAN MLPAHVFMRF YIIIASFIKL FSLFRHVAYG CSKPGCLFCY KRNRSLRVKC STIVGGMIRY YDVMANGGTG FCSKHQWNCI DCESYKPGNT FITVEAALDL SKELKRPIQP TDVAYHTVTD VKQVGCYMRL FYERDGQRTY DDVNASLFVD YSNLLHSKVK GVPNMHVVVV ENDADKANFL NAAVFYAQSL FRPILMVDKN LITTANTGTS VTETMFDVYV DTFLSMFDVD KKSLNALIAT AHSSIKQGTQ ICKVLDTFLS CARKSCSIDS DVDTKCLADS VMSAVSAGLE LTDESCNNLV PTYLKGDNIV AADLGVLIQN SAKHVQGNVA KIAGVSCIWS VDAFNQLSSD FQHKLKKACC KTGLKLKLTY NKQMANVSVL TTPFSLKGGA VFSYFVYVCF LLSLVCFIGL WCLMPTYTVH KSDFQLPVYA SYKVLDNGVI RDVSVEDVCF ANKFEQFDQW YESTFGLSYY SNSMACPIVV AVVDQDFGST VFNVPTKVLR YGYHVLHFIT HALSADGVQC YTPHSQISYF NFYASGCVLS SACTMFAMAD GSPQPYCYTE GLMQNASLYS SLVPHVRYNL ANAKGFIRFP EVLREGLVRV VRTRSMSYCR VGLCEEADEG ICFNFNGSWV LNNDYYRSLP GTFCGRDVFD LIYQLFKGLA QPVDFLALTA SSIAGAILAV IVVLVFYYLI KLKRAFGDYT SIVFVNVIVW CVNFMMLFVF QVYPTLSCVY AICYFYATLY FPSEISVIMH LQWLVMYGTI MPLWFCLLYI SVVVSNHAFW VFAYCRRLGT SVRSDGTFEE MALTTFMITK DSYCKLKNSL SDVAFNRYLS LYNKYRYYSG KMDTAAYREA ACSQLAKAMD TFTNNNGSDV LYQPPTASVS TSFLQSGIVK MVNPTSKVEP CIVSVTYGNM TLNGLWLDDK VYCPRHVICS VSDMTNPDYT NLLCRVTSSD FTVLFDRLSL TVMSYQMQGC MLVLTVTLQN SRTPKYTFGV VKPGETFTVL AAYNGKPQGA FHVTMRSSYT IKGSFLCGSC GSVGYVLMGD CVKFVYMHQL ELSTGCHTGT DFNGDFYGPY KDAQVVQLPV QDYIQSVNFV AWLYAAILNN CNWFVQSDKC SVEDFNVWAL SNGFSQVKSD LVIDALASMT GVSLETLLAA IKRLKNGFQG RQIMGSCSFE DELTPSDVYQ QLAGIKLQSK RTRLVKGIVC WIMASTFLFS CIITAFVKWT MFMYVTTNML SITFCALCVI SLAMLLVKHK HLYLTMYIIP VLFTLLYNNY LVVYKQTFRG YVYAWLSYYV PSVEYTYTDE VIYGMLLLIG MVFVTLRSIN HDLFSFIMFV GRVISVVSLW YMGSNLEEEI LLMLASLFGT YTWTTALSMA AAKVIAKWVA VNVLYFTDIP QIKIVLVCYL FIGYIISCYW GLFSLMNSLF RMPLGVYNYK ISVQELRYMN ANGLRPPKNS FEALMLNFKL LGIGGVPIIE VSQFQSKLTD VKCANVVLLN CLQHLHVASN SKLWQYCSTL HNEILATSDL GVAFEKLAQL LIVLFANPAA VDSKCLTSIE EVCDDYAKDN TVLQALQSEF VNMASFVEYE VAKKNLDEAR SSGSANQQQL KQLEKACNIA KSAYERDRAV ARKLERMADL ALTNMYKEAR INDKKSKVVS ALQTMLFSMV RKLDNQALNS ILDNAVKGCV PLNAIPSLAA NTLTIIVPDK SVYDQVVDNV YVTYAGNVWQ IQTIQDSDGT NKQLNEISDD CNWPLVIIAN RHNEVSATVL QNNELMPAKL KTQVVNSGPD QTCNTPTQCY YNNSNNGKIV YAILSDVDGL KYTKILKDDG NFVVLELDPP CKFTVQDVKG LKIKYLYFVK GCNTLARGWV VGTISSTVRL QAGTATEYAS NSSILSLCAF SVDPKKTYLD FIQQGGTPIA NCVKMLCDHA GTGMAITVKP DATTNQDSYG GASVCIYCRA RVEHPDVDGL CKLRGKFVQV PVGIKDPVSY VLTHDVCQVC GFWRDGSCSC VSTDTTVQSK DTNFLNRVRG TSVDARLVPC ASGLSTDVQL RAFDICNASV AGIGLHLKVN CCRFQRVDEN GDKLDRFFVV KRTDLTIYNR EMECYERVKD CKFVAEHDFF TFDVEGSRVP HIVRKDLTKY TMLDLCYALR HFDRNDCMLL CDILSIYAGC EQSYFTKKDW YDFVENPDII NVYKKLGPIF NRALVSATEF ADKLVEVGLV GILTLDNQDL NGKWYDFGDY VIAAPGCGVA IADSYYSYMM PMLTMCHALD CELYVNNAYR LFDLVQYDFT DYKLELFNKY FKHWSMPYHP NTVDCQDDRC IIHCANFNIL FSMVLPNTCF GPLVRQIFVD GVPFVVSIGY HYKELGIVMN MDVDTHRYRL SLKDLLLYAA DPALHVASAS ALYDLRTCCF SVAAITSGVK FQTVKPGNFN QDFYDFILSK GLLKEGSSVD LKHFFFTQDG NAAITDYNYY KYNLPTMVDI KQLLFVLEVV YKYFEIYDGG CIPASQVIVN NYDKSAGYPF NKFGKARLYY EALSFEEQDE IYAYTKRNVL PTLTQMNLKY AISAKNRART VAGVSILSTM TGRMFHQKCL KSIAATRGVP VVIGTTKFYG GWDDMLRRLI KDVDNPVLMG WDYPKCDRAM PNILRIVSSL VLARKHEACC SQSDRFYRLA NECAQVLSEI VMCGGCYYVK PGGTSSGDAT TAFANSVFNI CQAVSANVCA LMSCNGNKIE DLSIRALQKR LYSHVYRSDV VDTTFVTEYY EFLNKHFSMM ILSDDGVVCY NSDYASKGYI ANISAFQQVL YYQNNVFMSE SKCWVENDIN NGPHEFCSQH TMLVKMDGDD VYLPYPDPSR ILGAGCFVDD LLKTDSVLLI ERFVSLAIDA YPLVYHENEE YQKVFRVYLE YIKKLYNDLG NQILDSYSVI LSTCDGQKFT DESFYKNMYL RSAVMQSVGA CVVCSSQTSL RCGSCIRKPL LCCKCCYDHV MATDHKYVLS VSPYVCNAPG CDVNDVTKLY LGGMSYYCED HKPQYSFKLV MNGMVFGLYK QSCTGSPYID DFNRIASCKW TDVDDYILAN ECTERLKLFA AETQKATEEA FKQSYASATI QEIVSERELI LSWEIGKVKP PLNKNYVFTG YHFTKNGKTV LGEYVFDKSE LTNGVYYRAT TTYKLSVGDV FVLTSHSVAN LSAPTLVPQE NYSSIRFASV YSVLETFQNN VVNYQHIGMK RYCTVQGPPG TGKSHLAIGL AVYYCTARVV YTAASHAAVD ALCEKAYKFL NINDCTRIVP AKVRVECYDK FKINDTTRKY VFTTINALPE MVTDIVVVDE VSMLTNYELS VINARIRAKH YVYIGDPAQL PAPRVLLSKG TLEPKYFNTV TKLMCCLGPD IFLGTCYRCP KEIVDTVSAL VYENKLKAKN ESSSLCFKVY YKGVTTHESS SAVNMQQIYL INKFLKANPL WHKAVFISPY NSQNFAAKRV LGLQTQTVDS AQGSEYDYVI YSQTAETAHS VNVNRFNVAI TRAKKGILCV MSNMQLFEAL QFTTLTLDKV PQAVETRVQC STNLFKDCSK SYSGYHPAHA PSFLAVDDKY KATGDLAVCL GIGDSAVTYS RLISLMGFKL DVTLDGYCKL FITKEEAVKR VRAWVGFDAE GAHATRDSIG TNFPLQLGFS TGIDFVVEAT GLFADRDGYS FKKAVAKAPP GEQFKHLIPL MTRGQRWDVV RPRIVQMFAD HLIDLSDCVV LVTWAANFEL TCLRYFAKVG REISCNVCTK RATAYNSRTG YYGCWRHSVT CDYLYNPLIV DIQQWGYTGS LSSNHDLYCS VHKGAHVASS DAIMTRCLAV YDCFCNNINW NVEYPIISNE LSINTSCRVL QRVMLKAAML CNRYTLCYDI GNPKAIACVK DFDFKFYDAQ PIVKSVKTLL YSFEAHKDSF KDGLCMFWNC NVDKYPPNAV VCRFDTRVLN NLNLPGCNGG SLYVNKHAFH TKPFSRAAFE HLKPMPFFYY SDTPCVYMDG MDAKQVDYVP LKSATCITRC NLGGAVCLKH AEEYREYLES YNTATTAGFT FWVYKTFDFY NLWNTFTKLQ SLENVVYNLV KTGHYTGQAG EMPCAIINDK VVAKIDKEDV VIFINNTTYP TNVAVELFAK RSIRHHPELK LFRNLNIDVC WKHVIWDYAR ESIFCSNTYG VCMYTDLKFI DKLNVLFDGR DNGALEAFKR SNNGVYISTT KVKSLSMIKG PPRAELNGVV VDKVGDTDCV FYFAVRKEGQ DVIFSQFDSL RVSSNQSPQG NLGSNEPGNV GGNDALATST IFTQSRVISS FTCRTDMEKD FIALDQHVFI QKYGLEDYAF EHIVYGNFNQ KIIGGLHLLI GLYRRHQTSN LVIQEFVSYD SSIHSYFITD GKSGGSKSVC TVIDILLDDF VALVKSLNLS CVSKVVNVNV DFKDFQFMLW CNDEKVMTFY PRLQAASDWK PGYSMPVLYK YLNSPMERVS LWNYGKPVTL PTGCMMNVAK YTQLCQYLNT TTLAVPVNMR VLHLGAGSEK GVAPGSAVLR QWLPAGTILV DNDLYPFVSD SVATYFGDCI TLPFDCQWDL IISDMYDPIT KNIGEYNVSK DGFFTYISYM IRDKLALGGS VAIKITEFSW NAELYKLMGY FAFWTVFCTN ANASSSEGFL IGINYLGKPK VEIDGSVMHA NYLFWRNSTV WNGGAYSLFD MAKFPLKLAG TAVINLRADQ INDMVYSLLE KGKLLVRDTN KEVFVGDSLV NVI //