R1A_CVHN1
ID R1A_CVHN1 Reviewed; 4471 AA.
AC P0C6U3; Q5MQD2;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Replicase polyprotein 1a;
DE Short=pp1a;
DE AltName: Full=ORF1a polyprotein;
DE Contains:
DE RecName: Full=Non-structural protein 1;
DE Short=nsp1;
DE AltName: Full=p28;
DE Contains:
DE RecName: Full=Non-structural protein 2;
DE Short=nsp2;
DE AltName: Full=p65;
DE Contains:
DE RecName: Full=Non-structural protein 3;
DE Short=nsp3;
DE EC=3.4.19.12;
DE EC=3.4.22.69;
DE AltName: Full=PL1-PRO/PL2-PRO;
DE AltName: Full=PL1/PL2;
DE AltName: Full=Papain-like proteinases 1/2;
DE AltName: Full=p210;
DE Contains:
DE RecName: Full=Non-structural protein 4;
DE Short=nsp4;
DE AltName: Full=Peptide HD2;
DE AltName: Full=p44;
DE Contains:
DE RecName: Full=3C-like proteinase;
DE Short=3CL-PRO;
DE Short=3CLp;
DE EC=3.4.22.-;
DE AltName: Full=M-PRO;
DE AltName: Full=nsp5;
DE AltName: Full=p27;
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 AltName: Full=p10;
DE Contains:
DE RecName: Full=Non-structural protein 8;
DE Short=nsp8;
DE AltName: Full=p22;
DE Contains:
DE RecName: Full=Non-structural protein 9;
DE Short=nsp9;
DE AltName: Full=p12;
DE Contains:
DE RecName: Full=Non-structural protein 10;
DE Short=nsp10;
DE AltName: Full=Growth factor-like peptide;
DE Short=GFL;
DE AltName: Full=p15;
DE Contains:
DE RecName: Full=Non-structural protein 11;
DE Short=nsp11;
GN ORFNames=1a;
OS Human coronavirus HKU1 (isolate N1) (HCoV-HKU1).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae;
OC Betacoronavirus; Embecovirus.
OX NCBI_TaxID=443239;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=15613317; DOI=10.1128/jvi.79.2.884-895.2005;
RA Woo P.C.Y., Lau S.K.P., Chu C.-M., Chan K.-H., Tsoi H.-W., Huang Y.,
RA Wong B.H.L., Poon R.W.S., Cai J.J., Luk W.-K., Poon L.L.M., Wong S.S.Y.,
RA Guan Y., Peiris J.S.M., Yuen K.-Y.;
RT "Characterization and complete genome sequence of a novel coronavirus,
RT coronavirus HKU1, from patients with pneumonia.";
RL J. Virol. 79:884-895(2005).
CC -!- FUNCTION: The papain-like proteinase 1 (PL1-PRO) and papain-like
CC proteinase 2 (PL2-PRO) are responsible for the cleavages located at the
CC N-terminus of the replicase polyprotein. In addition, PLP2 possesses a
CC deubiquitinating/deISGylating activity and processes both 'Lys-48'- and
CC 'Lys-63'-linked polyubiquitin chains from cellular substrates.
CC Antagonizes innate immune induction of type I interferon by blocking
CC the phosphorylation, dimerization and subsequent nuclear translocation
CC of host IRF-3 (By similarity). {ECO:0000250}.
CC -!- FUNCTION: [3C-like proteinase]: Responsible for the majority of
CC cleavages as it cleaves the C-terminus of replicase polyprotein at 11
CC sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-
CC [SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-
CC CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function
CC (By similarity). {ECO:0000255|PROSITE-ProRule:PRU00772}.
CC -!- FUNCTION: Nsp7-nsp8 hexadecamer may possibly confer processivity to the
CC polymerase, maybe by binding to dsRNA or by producing primers utilized
CC by the latter. {ECO:0000250}.
CC -!- FUNCTION: Nsp9 is a ssRNA-binding protein. {ECO:0000250}.
CC -!- FUNCTION: [Non-structural protein 1]: Binds to the 40S ribosomal
CC subunit and inhibits host translation. The nsp1-40S ribosome complex
CC further induces an endonucleolytic cleavage near the 5'UTR of host
CC mRNAs, targeting them for degradation. 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}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=TSAVLQ-|-SGFRK-NH2 and SGVTFQ-|-GKFKK the two peptides
CC corresponding to the two self-cleavage sites of the SARS 3C-like
CC proteinase are the two most reactive peptide substrates. The enzyme
CC exhibits a strong preference for substrates containing Gln at P1
CC position and Leu at P2 position.; EC=3.4.22.69;
CC -!- 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;
CC -!- SUBUNIT: 3CL-PRO exists as monomer and homodimer. Eight copies of nsp7
CC and eight copies of nsp8 assemble to form a heterohexadecamer. Nsp9 is
CC a dimer. Nsp10 forms a dodecamer (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 3]: Host membrane
CC {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4]: Host membrane
CC {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 6]: Host membrane
CC {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 7]: Host cytoplasm, host
CC perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC they merge into confluent complexes.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 8]: Host cytoplasm, host
CC perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC they merge into confluent complexes.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 9]: Host cytoplasm, host
CC perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC they merge into confluent complexes.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 10]: Host cytoplasm, host
CC perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC they merge into confluent complexes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=2;
CC Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC IsoId=P0C6U3-1; Sequence=Displayed;
CC Name=Replicase polyprotein 1ab; Synonyms=pp1ab;
CC IsoId=P0C6X2-1; 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.
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 (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: Isolate N1 belongs to genotype A.
CC -!- MISCELLANEOUS: [Isoform Replicase polyprotein 1a]: Produced by
CC conventional translation.
CC -!- SIMILARITY: Belongs to the coronaviruses polyprotein 1ab family.
CC {ECO:0000305}.
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DR EMBL; AY597011; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR PDB; 3D23; X-ray; 2.50 A; A/B/C/D=3335-3634.
DR PDBsum; 3D23; -.
DR SMR; P0C6U3; -.
DR SABIO-RK; P0C6U3; -.
DR EvolutionaryTrace; P0C6U3; -.
DR Proteomes; UP000008170; Genome.
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:0004843; F:cysteine-type deubiquitinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0008242; F:omega peptidase activity; IEA:InterPro.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:InterPro.
DR GO; GO:0003727; F:single-stranded RNA binding; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO: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:0039648; P:modulation by virus 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:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0039548; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity; IEA:UniProtKB-KW.
DR GO; GO:0019079; P:viral genome replication; IEA:InterPro.
DR GO; GO:0019082; P:viral protein processing; IEA:InterPro.
DR CDD; cd21560; betaCoV-Nsp6; 1.
DR CDD; cd21666; betaCoV_Nsp5_Mpro; 1.
DR CDD; cd21519; cv_beta_Nsp2_MHV-like; 1.
DR CDD; cd21473; cv_Nsp4_TM; 1.
DR CDD; cd21557; Macro_X_Nsp3-like; 1.
DR CDD; cd21467; Ubl1_cv_Nsp3_N-like; 1.
DR CDD; cd21466; Ubl2_cv_PLpro_N_Nsp3-like; 1.
DR Gene3D; 1.10.150.420; -; 1.
DR Gene3D; 1.10.1840.10; -; 1.
DR Gene3D; 1.10.8.1190; -; 2.
DR Gene3D; 1.10.8.370; -; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.40.10.250; -; 1.
DR Gene3D; 2.60.120.1680; -; 1.
DR Gene3D; 3.10.20.350; -; 1.
DR Gene3D; 3.10.20.540; -; 1.
DR Gene3D; 3.30.70.3540; -; 1.
DR Gene3D; 3.40.220.10; -; 1.
DR Gene3D; 3.40.50.11020; -; 1.
DR InterPro; IPR022570; B-CoV_A_NSP1.
DR InterPro; IPR043613; CoV_NSP2_C.
DR InterPro; IPR043611; CoV_NSP3_C.
DR InterPro; IPR032505; CoV_NSP4_C.
DR InterPro; IPR043612; CoV_NSP4_N.
DR InterPro; IPR022733; DPUP_SUD_C_bCoV.
DR InterPro; IPR002589; Macro_dom.
DR InterPro; IPR043472; Macro_dom-like.
DR InterPro; IPR044371; Macro_X_NSP3-like.
DR InterPro; IPR036333; NSP10_sf_CoV.
DR InterPro; IPR044384; NSP2_MHV-like.
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; 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; IPR018995; RNA_synth_NSP10_CoV.
DR Pfam; PF16251; bCoV_NAR; 1.
DR Pfam; PF09401; CoV_NSP10; 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; PF11963; DUF3477; 1.
DR Pfam; PF01661; Macro; 1.
DR Pfam; PF01831; Peptidase_C16; 1.
DR Pfam; PF05409; Peptidase_C30; 1.
DR SMART; SM00506; A1pp; 1.
DR SUPFAM; SSF101816; SSF101816; 1.
DR SUPFAM; SSF140367; SSF140367; 1.
DR SUPFAM; SSF143076; SSF143076; 1.
DR SUPFAM; SSF144246; SSF144246; 1.
DR SUPFAM; SSF159936; SSF159936; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF52949; SSF52949; 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; PS51962; COV_NSP1; 1.
DR PROSITE; PS51991; COV_NSP2_C; 1.
DR PROSITE; PS51990; COV_NSP2_M; 1.
DR PROSITE; PS51989; COV_NSP2_N; 1.
DR PROSITE; PS51992; COV_NSP3_Y3; 1.
DR PROSITE; PS51943; COV_NSP3A_UBL; 1.
DR PROSITE; PS51944; COV_NSP3D_UBL; 1.
DR PROSITE; PS51946; COV_NSP4C; 1.
DR PROSITE; PS51949; COV_NSP7; 1.
DR PROSITE; PS51950; COV_NSP8; 1.
DR PROSITE; PS51951; COV_NSP9_SSRNA_BD; 1.
DR PROSITE; PS51442; M_PRO; 1.
DR PROSITE; PS51154; MACRO; 1.
DR PROSITE; PS51124; PEPTIDASE_C16; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Activation of host autophagy by virus;
KW Decay of host mRNAs by virus;
KW Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host translation shutoff by virus; Host cytoplasm;
KW 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 IRF3 by virus; Inhibition of host ISG15 by virus;
KW Inhibition of host RLR pathway by virus; Membrane; Metal-binding;
KW Modulation of host ubiquitin pathway by viral deubiquitinase;
KW Modulation of host ubiquitin pathway by virus; Protease; Repeat;
KW Ribosomal frameshifting; RNA-binding; Thiol protease; Transmembrane;
KW Transmembrane helix; Ubl conjugation pathway; Viral immunoevasion; Zinc;
KW Zinc-finger.
FT CHAIN 1..4471
FT /note="Replicase polyprotein 1a"
FT /id="PRO_0000338194"
FT CHAIN 1..222
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000338195"
FT CHAIN 223..809
FT /note="Non-structural protein 2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000338196"
FT CHAIN 810..2838
FT /note="Non-structural protein 3"
FT /evidence="ECO:0000250"
FT /id="PRO_0000338197"
FT CHAIN 2839..3334
FT /note="Non-structural protein 4"
FT /evidence="ECO:0000250"
FT /id="PRO_0000338198"
FT CHAIN 3335..3637
FT /note="3C-like proteinase"
FT /evidence="ECO:0000250"
FT /id="PRO_0000338199"
FT CHAIN 3638..3924
FT /note="Non-structural protein 6"
FT /evidence="ECO:0000250"
FT /id="PRO_0000338200"
FT CHAIN 3925..4016
FT /note="Non-structural protein 7"
FT /evidence="ECO:0000250"
FT /id="PRO_0000338201"
FT CHAIN 4017..4210
FT /note="Non-structural protein 8"
FT /evidence="ECO:0000250"
FT /id="PRO_0000338202"
FT CHAIN 4211..4320
FT /note="Non-structural protein 9"
FT /evidence="ECO:0000250"
FT /id="PRO_0000338203"
FT CHAIN 4321..4457
FT /note="Non-structural protein 10"
FT /evidence="ECO:0000250"
FT /id="PRO_0000338204"
FT CHAIN 4458..4471
FT /note="Non-structural protein 11"
FT /evidence="ECO:0000255"
FT /id="PRO_0000338205"
FT TRANSMEM 2226..2246
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2287..2307
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2318..2338
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2401..2421
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2443..2463
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2844..2864
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3119..3139
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3151..3171
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3178..3198
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3203..3223
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3651..3671
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3676..3696
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3701..3721
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3744..3764
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3772..3792
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3800..3820
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 3843..3863
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 54..174
FT /note="CoV Nsp1 globular"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01307"
FT DOMAIN 192..222
FT /note="BetaCoV Nsp1 C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01308"
FT DOMAIN 226..488
FT /note="CoV Nsp2 N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT DOMAIN 493..681
FT /note="CoV Nsp2 middle"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01334"
FT DOMAIN 697..809
FT /note="CoV Nsp2 C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01335"
FT DOMAIN 811..923
FT /note="Ubiquitin-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT REPEAT 945..954
FT /note="1"
FT REPEAT 955..964
FT /note="2"
FT REPEAT 965..974
FT /note="3"
FT REPEAT 975..984
FT /note="4"
FT REPEAT 985..994
FT /note="5"
FT REPEAT 995..1004
FT /note="6"
FT REPEAT 1005..1014
FT /note="7"
FT REPEAT 1015..1024
FT /note="8"
FT REPEAT 1025..1034
FT /note="9"
FT REPEAT 1035..1044
FT /note="10"
FT REPEAT 1045..1054
FT /note="11"
FT REPEAT 1055..1064
FT /note="12"
FT REPEAT 1065..1074
FT /note="13"
FT REPEAT 1075..1084
FT /note="14"
FT DOMAIN 1123..1373
FT /note="Peptidase C16 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT DOMAIN 1351..1522
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 1578..1649
FT /note="DPUP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01289"
FT DOMAIN 1649..1704
FT /note="Ubiquitin-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 1718..1978
FT /note="Peptidase C16 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT DOMAIN 1992..2093
FT /note="Nucleic acid-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01290"
FT DOMAIN 2108..2257
FT /note="G2M"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01338"
FT DOMAIN 2735..2838
FT /note="CoV Nsp3 Y3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT DOMAIN 3237..3334
FT /note="Nsp4C"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01291"
FT DOMAIN 3335..3637
FT /note="Peptidase C30"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT DOMAIN 3925..4013
FT /note="RdRp Nsp7 cofactor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01294"
FT DOMAIN 4014..4210
FT /note="RdRp Nsp8 cofactor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01295"
FT DOMAIN 4211..4320
FT /note="Nsp9 ssRNA-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01296"
FT DOMAIN 4321..4458
FT /note="ExoN/MTase coactivator"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT ZN_FING 1238..1266
FT /note="C4-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ZN_FING 1835..1871
FT /note="C4-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ZN_FING 4394..4410
FT /evidence="ECO:0000250"
FT ZN_FING 4436..4449
FT /evidence="ECO:0000250"
FT REGION 365..389
FT /note="C4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT REGION 945..1084
FT /note="14 X 10 AA tandem repeat of N-[DN]-D-E-D-V-V-T-G-D"
FT REGION 946..1064
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2226..2463
FT /note="HD1"
FT /evidence="ECO:0000250"
FT REGION 2844..3223
FT /note="HD2"
FT /evidence="ECO:0000250"
FT REGION 3651..3863
FT /note="HD3"
FT /evidence="ECO:0000250"
FT ACT_SITE 1161
FT /note="For PL1-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ACT_SITE 1312
FT /note="For PL1-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ACT_SITE 1757
FT /note="For PL2-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ACT_SITE 1914
FT /note="For PL2-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT ACT_SITE 3375
FT /note="For 3CL-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT ACT_SITE 3479
FT /note="For 3CL-PRO activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT BINDING 365
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT BINDING 370
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT BINDING 386
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT BINDING 389
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT BINDING 4394
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4397
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4403
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4410
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4436
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4439
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4447
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT BINDING 4449
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT SITE 222..223
FT /note="Cleavage; by PL1-PRO"
FT /evidence="ECO:0000250"
FT SITE 809..810
FT /note="Cleavage; by PL1-PRO"
FT /evidence="ECO:0000250"
FT SITE 2838..2839
FT /note="Cleavage; by PL2-PRO"
FT /evidence="ECO:0000250"
FT SITE 3334..3335
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000250"
FT SITE 3637..3638
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000250"
FT SITE 3924..3925
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000250"
FT SITE 4016..4017
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000250"
FT SITE 4210..4211
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000250"
FT SITE 4320..4321
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000250"
FT SITE 4457..4458
FT /note="Cleavage; by 3CL-PRO"
FT /evidence="ECO:0000250"
FT TURN 3345..3347
FT /evidence="ECO:0007829|PDB:3D23"
FT HELIX 3348..3350
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3351..3356
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3359..3366
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3369..3373
FT /evidence="ECO:0007829|PDB:3D23"
FT HELIX 3374..3377
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3380..3382
FT /evidence="ECO:0007829|PDB:3D23"
FT HELIX 3388..3394
FT /evidence="ECO:0007829|PDB:3D23"
FT HELIX 3397..3399
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3400..3404
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3407..3409
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3411..3417
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3420..3427
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3434..3437
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3445..3452
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3455..3463
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3482..3485
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3491..3502
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3505..3509
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3521..3524
FT /evidence="ECO:0007829|PDB:3D23"
FT HELIX 3535..3547
FT /evidence="ECO:0007829|PDB:3D23"
FT HELIX 3561..3571
FT /evidence="ECO:0007829|PDB:3D23"
FT HELIX 3580..3589
FT /evidence="ECO:0007829|PDB:3D23"
FT HELIX 3593..3604
FT /evidence="ECO:0007829|PDB:3D23"
FT STRAND 3615..3617
FT /evidence="ECO:0007829|PDB:3D23"
FT HELIX 3624..3632
FT /evidence="ECO:0007829|PDB:3D23"
SQ SEQUENCE 4471 AA; 502589 MW; 6A17587F5DF95C46 CRC64;
MIKTSKYGLG FKWAPEFRWL LPDAAEELAS PMKSDEGGLC PSTGQAMESV GFVYDNHVKI
DCRCILGQEW HVQSNLIRDI FVHEDLHVVE VLTKTAVKSG TAILIKSPLH SLGGFPKGYV
MGLFRSYKTK RYVVHHLSMT TSTTNFGEDF LGWIVPFGFM PSYVHKWFQF CRLYIEESDL
IISNFKFDDY DFSVEDAYAE VHAEPKGKYS QKAYALLRQY RGIKPVLFVD QYGCDYSGKL
ADCLQAYGHY SLQDMRQKQS VWLANCDFDI VVAWHVVRDS RFVMRLQTIA TICGIKYVAQ
PTEDVVDGDV VIREPVHLLS ADAIVLKLPS LMKVMTHMDD FSIKSIYNVD LCDCGFVMQY
GYVDCFNDNC DFYGWVSGNM MDGFSCPLCC TVYDSSEVKA QSSGVIPENP VLFTNSTDTV
NHDSFNLYGY SVTPFGSCIY WSPRPGLWIP IIKSSVKSYD DLVYSGVVGC KSIVKETALI
THALYLDYVQ CKCGNLEQNH ILGVNNSWCR QLLLNRGDYN MLLKNIDLFV KRRADFACKF
AVCGDGFVPF LLDGLIPRSY YLIQSGIFFT SLMSQFSQEV SDMCLKMCIL FMDRVSVATF
YIEHYVNRLV TQFKLLGTTL VNKMVNWFNT MLDASAPATG WLLYQLLNGL FVVSQANFNF
VALIPDYAKI LVNKFYTFFK LLLECVTVDV LKDMPVLKTI NGLVCIVGNK FYNVSTGLIP
GFVLPCNAQE QQIYFFEGVA ESVIVEDDVI ENVKSSLSSY EYCQPPKSVE KICIIDNMYM
GKCGDKFFPI VMNDKNICLL DQAWRFPCAG RKVNFNEKPV VMEIPSLMTV KVMFDLDSTF
DDILGKVCSE FEVEKGVTVD DFVAVVCDAI ENALNSCKEH PVVGYQVRAF LNKLNENVVY
LFDEAGDEAM ASRMYCTFAI EDVEDVISSE AVEDTIDGVV EDTINDDEDV VTGDNDDEDV
VTGDNDDEDV VTGDNDDEDV VTGDNDDEDV VTGDNDDEDV VTGDNDDEDV VTGDNDDEDV
VTGDNDDEDV VTGDNDDEDV VTGDNDDEDV VTGDNDDEDV VTGDNDDEDV VTGDNDDEDV
VTGDNNDEEI VTGDNDDQIV VTGDDVDDIE SIYDFDTYKA LLVFNDVYND ALFVSYGSSV
ETETYFKVNG LWSPTITHTN CWLRSVLLVM QKLPFKFKDL AIENMWLSYK VGYNQSFVDY
LLTTIPKAIV LPQGGFVADF AYWFLNQFDI NAYANWCCLK CGFSFDLNGL DALFFYGDIV
SHVCKCGHNM TLIAADLPCT LHFSLFDDNF CAFCTPKKIF IAACAVDVNV CHSVAVIGDE
QIDGKFVTKF SGDKFDFIVG YGMSFSMSSF ELPQLYGLCI TPNVCFVKGD IINVARLVKA
DVIVNPANGH MLHGGGVAKA IAVAAGKKFS KETAAMVKSK GVCQVGDCYV STGGKLCKTI
LNIVGPDARQ DGRQSYVLLA RAYKHLNNYD CCLSTLISAG IFSVPADVSL TYLLGVVDKQ
VILVSNNKED FDIIQKCQIT SVVGTKALAV RLTANVGRVI KFETDAYKLF LSGDDCFVSN
SSVIQEVLLL RHDIQLNNDV RDYLLSKMTS LPKDWRLINK FDVINGVKTV KYFECPNSIY
ICSQGKDFGY VCDGSFYKAT VNQVCVLLAK KIDVLLTVDG VNFKSISLTV GEVFGKILGN
VFCDGIDVTK LKCSDFYADK ILYQYENLSL ADISAVQSSF GFDQQQLLAY YNFLTVCKWS
VVVNGPFFSF EQSHNNCYVN VACLMLQHIN LKFNKWQWQE AWYEFRAGRP HRLVALVLAK
GHFKFDEPSD ATDFIRVVLK QADLSGAICE LELICDCGIK QESRVGVDAV MHFGTLAKTD
LFNGYKIGCN CAGRIVHCTK LNVPFLICSN TPLSKDLPDD VVAANMFMGV GVGHYTHLKC
GSPYQHYDAC SVKKYTGVSG CLTDCLYLKN LTQTFTSMLT NYFLDDVEMV AYNPDLSQYY
CDNGKYYTKP IIKAQFKPFA KVDGVYTNFK LVGHDICAQL NDKLGFNVDL PFVEYKVTVW
PVATGDVVLA SDDLYVKRYF KGCETFGKPV IWFCHDEASL NSLTYFNKPS FKSENRYSVL
SVDSVSEESQ GNVVTSVMES QISTKEVKLK GVRKTVKIED AIIVNDENSS IKVVKSLSLV
DVWDMYLTGC DYVVWVANEL SRLVKSPTVR EYIRYGIKPI TIPIDLLCLR DDNQTLLVPK
IFKARAIEFY GFLKWLFIYV FSLLHFTNDK TIFYTTEIAS KFTFNLFCLA LKNAFQTFRW
SIFIKGFLVV ATVFLFWFNF LYINVIFSDF YLPNISVFPI FVGRIVMWIK ATFGLVTICD
FYSKLGVGFT SHFCNGSFIC ELCHSGFDML DTYAAIDFVQ YEVDRRVLFD YVSLVKLIVE
LVIGYSLYTV WFYPLFCLIG LQLFTTWLPD LFMLETMHWL IRFIVFVANM LPAFVLLRFY
IVVTAMYKVV GFIRHIVYGC NKAGCLFCYK RNCSVRVKCS TIVGGVIRYY DITANGGTGF
CVKHQWNCFN CHSFKPGNTF ITVEAAIELS KELKRPVNPT DASHYVVTDI KQVGCMMRLF
YDRDGQRVYD DVDASLFVDI NNLLHSKVKV VPNLYVVVVE SDADRANFLN AVVFYAQSLY
RPILLVDKKL ITTACNGISV TQTMFDVYVD TFMSHFDVDR KSFNNFVNIA HASLREGVQL
EKVLDTFVGC VRKCCSIDSD VETRFITKSM ISAVAAGLEF TDENYNNLVP TYLKSDNIVA
ADLGVLIQNG AKHVQGNVAK AANISCIWFI DAFNQLTADL QHKLKKACVK TGLKLKLTFN
KQEASVPILT TPFSLKGGVV LSNLLYILFF VSLICFILLW ALLPTYSVYK SDIHLPAYAS
FKVIDNGVVR DISVNDLCFA NKFFQFDQWY ESTFGSVYYH NSMDCPIVVA VMDEDIGSTM
FNVPTKVLRH GFHVLHFLTY AFASDSVQCY TPHIQISYND FYASGCVLSS LCTMFKRGDG
TPHPYCYSDG VMKNASLYTS LVPHTRYSLA NSNGFIRFPD VISEGIVRIV RTRSMTYCRV
GACEYAEEGI CFNFNSSWVL NNDYYRSMPG TFCGRDLFDL FYQFFSSLIR PIDFFSLTAS
SIFGAILAIV VVLVFYYLIK LKRAFGDYTS VVVINVVVWC INFLMLFVFQ VYPICACVYA
CFYFYVTLYF PSEISVIMHL QWIVMYGAIM PFWFCVTYVA MVIANHVLWL FSYCRKIGVN
VCSDSTFEET SLTTFMITKD SYCRLKNSVS DVAYNRYLSL YNKYRYYSGK MDTAAYREAA
CSQLAKAMET FNHNNGNDVL YQPPTASVST SFLQSGIVKM VSPTSKIEPC IVSVTYGSMT
LNGLWLDDKV YCPRHVICSS SNMNEPDYSA LLCRVTLGDF TIMSGRMSLT VVSYQMQGCQ
LVLTVSLQNP YTPKYTFGNV KPGETFTVLA AYNGRPQGAF HVTMRSSYTI KGSFLCGSCG
SVGYVLTGDS VKFVYMHQLE LSTGCHTGTD FTGNFYGPYR DAQVVQLPVK DYVQTVNVIA
WLYAAILNNC AWFVQNDVCS TEDFNVWAMA NGFSQVKADL VLDALASMTG VSIETLLAAI
KRLYMGFQGR QILGSCTFED ELAPSDVYQQ LAGVKLQSKT KRFIKETIYW ILISTFLFSC
IISAFVKWTI FMYINTHMIG VTLCVLCFVS FMMLLVKHKH FYLTMYIIPV LCTLFYVNYL
VVYKEGFRGF TYVWLSYFVP AVNFTYVYEV FYGCILCVFA IFITMHSINH DIFSLMFLVG
RIVTLISMWY FGSNLEEDVL LFITAFLGTY TWTTILSLAI AKIVANWLSV NIFYFTDVPY
IKLILLSYLF IGYILSCYWG FFSLLNSVFR MPMGVYNYKI SVQELRYMNA NGLRPPRNSF
EAILLNLKLL GIGGVPVIEV SQIQSKLTDV KCANVVLLNC LQHLHVASNS KLWQYCSVLH
NEILSTSDLS VAFDKLAQLL IVLFANPAAV DTKCLASIDE VSDDYVQDST VLQALQSEFV
NMASFVEYEV AKKNLADAKN SGSVNQQQIK QLEKACNIAK SVYERDKAVA RKLERMADLA
LTNMYKEARI NDKKSKVVSA LQTMLFSMVR KLDNQALNSI LDNAVKGCVP LSAIPALAAN
TLTIVIPDKQ VFDKVVDNVY VTYAGSVWHI QTVQDADGIN KQLTDISVDS NWPLVIIANR
YNEVANAVMQ NNELMPHKLK IQVVNSGSDM NCNIPTQCYY NNGSSGRIVY AVLSDVDGLK
YTKIMKDDGN CVVLELDPPC KFSIQDVKGL KIKYLYFIKG CNTLARGWVV GTLSSTIRLQ
AGVATEYAAN SSILSLCAFS VDPKKTYLDY IQQGGVPIIN CVKMLCDHAG TGMAITIKPE
ATINQDSYGG ASVCIYCRAR VEHPDVDGIC KLRGKFVQVP LGIKDPILYV LTHDVCQVCG
FWRDGSCSCV GSSVAVQSKD LNFLNGFGVL V
