ID RPOA_PRRSB Reviewed; 3961 AA.
AC Q8B912; Q8B911;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 3.
DT 27-MAR-2024, entry version 126.
DE RecName: Full=Replicase polyprotein 1ab;
DE AltName: Full=ORF1ab polyprotein;
DE Contains:
DE RecName: Full=Nsp1;
DE EC=3.4.22.-;
DE Contains:
DE RecName: Full=Nsp1-alpha papain-like cysteine proteinase;
DE EC=3.4.22.-;
DE AltName: Full=PCP1-alpha;
DE Contains:
DE RecName: Full=Nsp1-beta papain-like cysteine proteinase;
DE EC=3.4.22.-;
DE AltName: Full=PCP1-beta;
DE Contains:
DE RecName: Full=Nsp2 cysteine proteinase;
DE EC=3.4.19.12;
DE EC=3.4.22.-;
DE AltName: Full=CP2;
DE Short=CP;
DE Contains:
DE RecName: Full=Non-structural protein 3;
DE Short=Nsp3;
DE Contains:
DE RecName: Full=Serine protease nsp4;
DE Short=3CLSP;
DE EC=3.4.21.-;
DE AltName: Full=3C-like serine proteinase;
DE AltName: Full=Nsp4;
DE Contains:
DE RecName: Full=Non-structural protein 5-6-7;
DE Short=Nsp5-6-7;
DE Contains:
DE RecName: Full=Non-structural protein 5;
DE Short=Nsp5;
DE Contains:
DE RecName: Full=Non-structural protein 6;
DE Short=Nsp6;
DE Contains:
DE RecName: Full=Non-structural protein 7-alpha;
DE Short=Nsp7-alpha;
DE Contains:
DE RecName: Full=Non-structural protein 7-beta;
DE Short=Nsp7-beta;
DE Contains:
DE RecName: Full=Non-structural protein 8;
DE Short=Nsp8;
DE Contains:
DE RecName: Full=RNA-directed RNA polymerase;
DE Short=Pol;
DE Short=RdRp;
DE EC=2.7.7.48;
DE AltName: Full=Nsp9;
DE Contains:
DE RecName: Full=Helicase nsp10;
DE Short=Hel;
DE EC=3.6.4.12;
DE EC=3.6.4.13;
DE AltName: Full=Nsp10;
DE Contains:
DE RecName: Full=Uridylate-specific endoribonuclease nsp11;
DE EC=4.6.1.-;
DE AltName: Full=Non-structural protein 11;
DE Short=Nsp11;
DE Contains:
DE RecName: Full=Non-structural protein 12;
DE Short=Nsp12;
GN Name=rep; ORFNames=1a-1b;
OS Porcine reproductive and respiratory syndrome virus (strain HB-1) (PRRSV).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Nidovirales; Arnidovirineae; Arteriviridae; Variarterivirinae;
OC Betaarterivirus; Ampobartevirus; Betaarterivirus suid 2.
OX NCBI_TaxID=300563;
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=15221535; DOI=10.1007/s00705-004-0292-0;
RA Gao Z.Q., Guo X., Yang H.C.;
RT "Genomic characterization of two Chinese isolates of porcine respiratory
RT and reproductive syndrome virus.";
RL Arch. Virol. 149:1341-1351(2004).
CC -!- FUNCTION: [Replicase polyprotein 1ab]: Contains the activities
CC necessary for the transcription of negative stranded RNA, leader RNA,
CC subgenomic mRNAs and progeny virion RNA as well as proteinases
CC responsible for the cleavage of the polyprotein into functional
CC products.
CC -!- FUNCTION: [Nsp1-alpha papain-like cysteine proteinase]: Inhibits host
CC IFN-beta production. Plays a role in the degradation of the host
CC transcriptional activator CREBBP protein. The degradation of host
CC CREBBP which is a key component of the IFN enhanceosome is likely
CC responsible for the inhibition of interferon mediated by Nsp1-alpha.
CC Participates also in the inhibition of host NF-kappa-B activation by
CC counteracting LUBAC-dependent induction of NF-kappa-B. Reduces host
CC NEMO ubiquitination by blocking the interaction between the two LUBAC
CC complex components RNF31 and SHARPIN. {ECO:0000250|UniProtKB:Q04561}.
CC -!- FUNCTION: [Nsp1-beta papain-like cysteine proteinase]: Plays a role in
CC blocking host mRNA nuclear export to the cytoplasm and subversion of
CC host protein synthesis (By similarity). Additionally, inhibits the
CC interferon-activated JAK/STAT signal transduction by mediating the
CC ubiquitination and subsequent proteasomal degradation of host KPNA1 (By
CC similarity). Repurposes the host antiviral stress granules into a
CC proviral platform to counteract the EIF2AK2/PKR restriction, thereby
CC regulating the host inflammatory response (By similarity).
CC {ECO:0000250|UniProtKB:A6YQT5, ECO:0000250|UniProtKB:Q04561,
CC ECO:0000250|UniProtKB:Q9WJB2}.
CC -!- FUNCTION: [Nsp2 cysteine proteinase]: Multifunctional protein that acts
CC as a viral protease and as a viral antagonist of host immune response.
CC Cleaves the nsp2/nsp3 site in the viral polyprotein. Displays
CC deubiquitinating activity that cleaves both ubiquitinated and ISGylated
CC products and therefore inhibits ubiquitin and ISG15-dependent host
CC innate immunity. Deubiquitinates also host NFKBIA, thereby interfering
CC with NFKBIA degradation and impairing subsequent NF-kappa-B activation.
CC {ECO:0000250|UniProtKB:A0MD28}.
CC -!- FUNCTION: [Non-structural protein 3]: Plays a role in the inhibition of
CC the immune response by interacting with host IFITM1. This interaction
CC leads to the proteasomal degradation of the IFN-induced antiviral
CC protein IFITM1. {ECO:0000250|UniProtKB:Q04561}.
CC -!- FUNCTION: [Serine protease nsp4]: Cleaves the majority of cleavage
CC sites present in the C-terminus of the polyprotein. Triggers host
CC apoptosis through caspase-3, -8, and -9 activations. Subverts host
CC innate immune responses through its protease activity. Targets the NF-
CC kappa-B essential modulator NEMO and mediates its cleavage. Blocks host
CC interferon beta induction and downstream signaling by cleaving
CC mitochondrial MAVS, dislodging it from the mitochondria. Impairs host
CC defense by cleaving host mRNA-decapping enzyme DCP1A to attenuate its
CC antiviral activity. {ECO:0000250|UniProtKB:Q04561}.
CC -!- FUNCTION: [Non-structural protein 5-6-7]: Plays a role in the initial
CC induction of autophagosomes from host reticulum endoplasmic.
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- FUNCTION: [Non-structural protein 5]: Plays a role in the inhibition of
CC host STAT3 signaling pathway by inducing the degradation of STAT3.
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- FUNCTION: [RNA-directed RNA polymerase]: Responsible for replication
CC and transcription of the viral RNA genome.
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- FUNCTION: [Helicase nsp10]: Displays RNA and DNA duplex-unwinding
CC activities with 5' to 3' polarity. {ECO:0000250|UniProtKB:Q04561}.
CC -!- FUNCTION: [Uridylate-specific endoribonuclease nsp11]: Plays a role in
CC viral transcription/replication and prevents the simultaneous
CC activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, PKR (By
CC similarity) and NLRP3 inflammasome (By similarity). Acts by degrading
CC the 5'-polyuridines generated during replication of the poly(A) region
CC of 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 (By similarity). Also
CC plays a role in the inhibition of host type I interferon production by
CC recruiting host OTULIN to promote removal of linear ubiquitination
CC targeting host NEMO (By similarity). {ECO:0000250|UniProtKB:P0C6X7,
CC ECO:0000250|UniProtKB:P19811, ECO:0000250|UniProtKB:Q04561}.
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:14527, Rhea:RHEA-
CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
CC -!- CATALYTIC ACTIVITY: [Helicase nsp10]:
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:Q04561};
CC -!- CATALYTIC ACTIVITY: [Helicase nsp10]:
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:Q04561};
CC -!- CATALYTIC ACTIVITY: [Nsp2 cysteine proteinase]:
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:0000250|UniProtKB:Q04561};
CC -!- CATALYTIC ACTIVITY: [Uridylate-specific endoribonuclease nsp11]:
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:0000250|UniProtKB:P19811};
CC -!- SUBUNIT: Nsp1-alpha papain-like: Interacts with host RNF31.
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBUNIT: [Nsp1-beta papain-like cysteine proteinase]: Interacts with
CC host EIF2AK2; this interaction occurs in host stress granules and leads
CC to EIF2AK2 inhibition. Interacts with host G3BP1; this interaction
CC probably plays a role in Nsp1-beta-mediated inhibition of host EIF2AK2.
CC {ECO:0000250|UniProtKB:A6YQT5}.
CC -!- SUBUNIT: [Nsp2 cysteine proteinase]: Interacts with host DDX18; this
CC interaction redistributes host DDX18 to the cytoplasm.
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBUNIT: [Non-structural protein 3]: Interacts with host IFITM1.
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase]: Interacts with host DDX5.
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBUNIT: [Helicase nsp10]: Interacts with host DDX18; this interaction
CC redistributes host DDX18 to the cytoplasm.
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBUNIT: [Uridylate-specific endoribonuclease nsp11]: Interacts with
CC host OTULIN. {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBUNIT: [Non-structural protein 12]: Interacts with host LGALS3.
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBCELLULAR LOCATION: [Nsp1]: Host nucleus
CC {ECO:0000250|UniProtKB:Q04561}. Host cytoplasm
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBCELLULAR LOCATION: [Nsp1-alpha papain-like cysteine proteinase]:
CC Host nucleus {ECO:0000250|UniProtKB:Q04561}. Host cytoplasm
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBCELLULAR LOCATION: [Nsp1-beta papain-like cysteine proteinase]: Host
CC nucleus {ECO:0000250|UniProtKB:A6YQT5}. Host cytoplasm
CC {ECO:0000250|UniProtKB:A6YQT5}. Note=Accumulates mainly in the host
CC cytoplasm in early infection and then mostly in the host nucleus.
CC {ECO:0000250|UniProtKB:A6YQT5}.
CC -!- SUBCELLULAR LOCATION: [Nsp2 cysteine proteinase]: Host cytoplasm
CC {ECO:0000250|UniProtKB:Q04561}. Host membrane
CC {ECO:0000250|UniProtKB:Q04561}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 5-6-7]: Host endoplasmic
CC reticulum {ECO:0000250|UniProtKB:Q04561}. Host membrane
CC {ECO:0000250|UniProtKB:Q04561}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBCELLULAR LOCATION: [Serine protease nsp4]: Host cytoplasm
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm
CC {ECO:0000250|UniProtKB:Q04561}. Host cytoplasm, host perinuclear region
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBCELLULAR LOCATION: [Helicase nsp10]: Host cytoplasm
CC {ECO:0000250|UniProtKB:Q04561}. Host cytoplasm, host perinuclear region
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBCELLULAR LOCATION: [Uridylate-specific endoribonuclease nsp11]: Host
CC cytoplasm {ECO:0000250|UniProtKB:Q04561}. Host nucleus
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 12]: Host cytoplasm
CC {ECO:0000250|UniProtKB:Q04561}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=2;
CC Name=Replicase polyprotein 1ab; Synonyms=pp1ab;
CC IsoId=Q8B912-1; Sequence=Displayed;
CC Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC IsoId=Q8B912-2; Sequence=VSP_032891;
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}.
CC -!- DOMAIN: The OTU-like region is responsible for the deubiquitinating and
CC deISGylation activities of Nsp2. {ECO:0000250}.
CC -!- PTM: [Replicase polyprotein 1ab]: Specific enzymatic cleavages in vivo
CC by its own proteases yield mature proteins. Nsp1 is autocleaved into
CC two subunits, Nsp1-alpha and Nsp1-beta. There are two alternative
CC pathways for processing. Either nsp4-5 is cleaved, which represents the
CC major pathway or the nsp5-6 and nsp6-7 are processed, which represents
CC the minor pathway. The major pathway occurs when nsp2 acts as a
CC cofactor for nsp4. {ECO:0000250|UniProtKB:Q9WJB2}.
CC -!- MISCELLANEOUS: [Isoform Replicase polyprotein 1ab]: Produced by -1
CC ribosomal frameshifting at the 1a-1b genes boundary.
CC -!- MISCELLANEOUS: [Isoform Replicase polyprotein 1a]: Produced by
CC conventional translation. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the arteriviridae polyprotein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAN73221.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY150312; AAN73220.1; -; mRNA.
DR EMBL; AY150312; AAN73221.1; ALT_INIT; mRNA.
DR SMR; Q8B912; -.
DR MEROPS; S32.002; -.
DR ABCD; Q8B912; 8 sequenced antibodies.
DR Proteomes; UP000124990; Genome.
DR GO; GO:0044165; C:host cell endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
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-KW.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0004540; F:RNA nuclease activity; IEA:UniProt.
DR GO; GO:0003968; F:RNA-dependent RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0039563; P:disruption by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro.
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: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:0039580; P:suppression by virus of host PKR signaling; 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:0019082; P:viral protein processing; IEA:InterPro.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR CDD; cd21410; 1B_av_Nsp10-like; 1.
DR CDD; cd23189; Arteriviridae_RdRp; 1.
DR CDD; cd22528; av_Nsp3_ER-remodelling; 1.
DR CDD; cd17937; DEXXYc_viral_SF1-N; 1.
DR CDD; cd21160; NendoU_av_Nsp11-like; 1.
DR CDD; cd21166; NTD_av_Nsp11-like; 1.
DR CDD; cd18786; SF1_C; 1.
DR CDD; cd21405; ZBD_av_Nsp10-like; 1.
DR Gene3D; 3.90.70.160; -; 1.
DR Gene3D; 4.10.80.390; -; 1.
DR Gene3D; 3.30.1330.220; Arterivirus nonstructural protein 7 alpha; 1.
DR Gene3D; 2.30.31.30; Arterivirus nps1beta, nuclease domain; 1.
DR Gene3D; 3.90.70.70; Arterivirus papain-like cysteine protease beta domain; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2.
DR Gene3D; 3.90.70.60; Porcine arterivirus-type cysteine proteinase alpha domain; 1.
DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR InterPro; IPR027351; (+)RNA_virus_helicase_core_dom.
DR InterPro; IPR031932; Arteri_nsp7a.
DR InterPro; IPR038451; Arteri_nsp7a_sf.
DR InterPro; IPR008743; Arterivirus_Nsp2_C33.
DR InterPro; IPR023338; Arterivirus_NSP4_peptidase.
DR InterPro; IPR046440; AV_NSP11N_COV_NSP15M.
DR InterPro; IPR008741; AV_PCPalpha.
DR InterPro; IPR038155; AV_PCPalpha_sf.
DR InterPro; IPR025773; AV_PCPbeta.
DR InterPro; IPR038154; AV_PCPbeta_sf.
DR InterPro; IPR023183; Chymotrypsin-like_C.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR008760; EAV_peptidase_S32.
DR InterPro; IPR037227; EndoU-like.
DR InterPro; IPR043609; NendoU_nidovirus.
DR InterPro; IPR044863; NIRAN.
DR InterPro; IPR044348; NSP10_1B_Av.
DR InterPro; IPR027355; NSP10_Av_ZBD.
DR InterPro; IPR044320; NSP11_Av_N.
DR InterPro; IPR044314; NSP11_NendoU_Av.
DR InterPro; IPR032855; NSP2-B_epitope.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR032785; Pdase_C33_assoc.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001205; RNA-dir_pol_C.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR Pfam; PF16749; Arteri_nsp7a; 1.
DR Pfam; PF19215; CoV_NSP15_C; 1.
DR Pfam; PF14757; NSP2-B_epitope; 1.
DR Pfam; PF14756; Pdase_C33_assoc; 1.
DR Pfam; PF05410; Peptidase_C31; 1.
DR Pfam; PF05411; Peptidase_C32; 1.
DR Pfam; PF05412; Peptidase_C33; 1.
DR Pfam; PF05579; Peptidase_S32; 1.
DR Pfam; PF00680; RdRP_1; 1.
DR Pfam; PF01443; Viral_helicase1; 1.
DR SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR SUPFAM; SSF142877; EndoU-like; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR PROSITE; PS51538; AV_CP; 1.
DR PROSITE; PS51961; AV_NSP11N_COV_NSP15M; 1.
DR PROSITE; PS51493; AV_NSP4_PRO; 1.
DR PROSITE; PS51539; AV_PCP_ALPHA; 1.
DR PROSITE; PS51540; AV_PCP_BETA; 1.
DR PROSITE; PS51652; AV_ZBD; 1.
DR PROSITE; PS51958; NENDOU; 1.
DR PROSITE; PS51947; NIRAN; 1.
DR PROSITE; PS51657; PSRV_HELICASE; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Endonuclease; Helicase; Host cytoplasm;
KW Host endoplasmic reticulum; Host membrane; Host nucleus;
KW 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 Inhibition of host PKR by virus; Inhibition of host STAT1 by virus;
KW Interferon antiviral system evasion; Lyase; Membrane; Metal-binding;
KW Modulation of host ubiquitin pathway by viral deubiquitinase;
KW Modulation of host ubiquitin pathway by virus; Multifunctional enzyme;
KW Nuclease; Nucleotide-binding; Nucleotidyltransferase; Protease;
KW Reference proteome; Ribosomal frameshifting; RNA-directed RNA polymerase;
KW Serine protease; Thiol protease; Transferase; Transmembrane;
KW Transmembrane helix; Viral immunoevasion; Viral RNA replication; Zinc;
KW Zinc-finger.
FT CHAIN 1..3961
FT /note="Replicase polyprotein 1ab"
FT /id="PRO_0000036670"
FT CHAIN 1..382
FT /note="Nsp1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000410827"
FT CHAIN 1..180
FT /note="Nsp1-alpha papain-like cysteine proteinase"
FT /evidence="ECO:0000255"
FT /id="PRO_0000036672"
FT CHAIN 181..383
FT /note="Nsp1-beta papain-like cysteine proteinase"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036673"
FT CHAIN 384..1579
FT /note="Nsp2 cysteine proteinase"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036674"
FT CHAIN 1580..1809
FT /note="Non-structural protein 3"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036675"
FT CHAIN 1810..2013
FT /note="Serine protease nsp4"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036676"
FT CHAIN 2014..2458
FT /note="Non-structural protein 5-6-7"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036677"
FT CHAIN 2014..2183
FT /note="Non-structural protein 5"
FT /evidence="ECO:0000250"
FT /id="PRO_0000423122"
FT CHAIN 2184..2199
FT /note="Non-structural protein 6"
FT /evidence="ECO:0000250"
FT /id="PRO_0000423123"
FT CHAIN 2200..2348
FT /note="Non-structural protein 7-alpha"
FT /evidence="ECO:0000250"
FT /id="PRO_0000423124"
FT CHAIN 2349..2458
FT /note="Non-structural protein 7-beta"
FT /evidence="ECO:0000250"
FT /id="PRO_0000423125"
FT CHAIN 2459..3144
FT /note="RNA-directed RNA polymerase"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036678"
FT CHAIN 2459..2503
FT /note="Non-structural protein 8"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036679"
FT CHAIN 3145..3585
FT /note="Helicase nsp10"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036680"
FT CHAIN 3586..3808
FT /note="Uridylate-specific endoribonuclease nsp11"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036681"
FT CHAIN 3809..3961
FT /note="Non-structural protein 12"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036682"
FT TRANSMEM 1266..1286
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1296..1316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1368..1388
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1583..1603
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1648..1668
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1685..1705
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1719..1739
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2036..2056
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2060..2080
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2092..2112
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2137..2157
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2162..2182
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 69..180
FT /note="Peptidase C31"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00872"
FT DOMAIN 263..383
FT /note="Peptidase C32"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00873"
FT DOMAIN 428..535
FT /note="Peptidase C33"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00871"
FT DOMAIN 1810..2013
FT /note="Peptidase S32"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT DOMAIN 2488..2651
FT /note="NiRAN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01292"
FT DOMAIN 2890..3024
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT DOMAIN 3145..3208
FT /note="AV ZBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT DOMAIN 3265..3417
FT /note="(+)RNA virus helicase ATP-binding"
FT DOMAIN 3418..3546
FT /note="(+)RNA virus helicase C-terminal"
FT DOMAIN 3585..3681
FT /note="AV-Nsp11N/CoV-Nsp15M"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01306"
FT DOMAIN 3683..3805
FT /note="NendoU"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT ZN_FING 8..28
FT /note="C4-type; atypical"
FT REGION 69..182
FT /note="PCP1-alpha"
FT REGION 199..200
FT /note="Important for host EIF2AK2 inhibition"
FT /evidence="ECO:0000250|UniProtKB:A6YQT5"
FT REGION 263..382
FT /note="PCP1-beta"
FT REGION 426..513
FT /note="OTU-like"
FT REGION 810..875
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 899..918
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1148..1191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1266..1388
FT /note="HD1"
FT REGION 1583..1745
FT /note="HD2"
FT REGION 2036..2157
FT /note="HD3"
FT COMPBIAS 825..840
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 76
FT /note="For Nsp1-alpha papain-like cysteine proteinase
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00872"
FT ACT_SITE 146
FT /note="For Nsp1-alpha papain-like cysteine proteinase
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00872"
FT ACT_SITE 270
FT /note="For Nsp1-beta papain-like cysteine proteinase
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00873"
FT ACT_SITE 339
FT /note="For Nsp1-beta papain-like cysteine proteinase
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00873"
FT ACT_SITE 437
FT /note="For Nsp2 cysteine proteinase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00871"
FT ACT_SITE 506
FT /note="For Nsp2 cysteine proteinase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00871"
FT ACT_SITE 1848
FT /note="Charge relay system; for 3C-like serine proteinase
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT ACT_SITE 1873
FT /note="Charge relay system; for 3C-like serine proteinase
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT ACT_SITE 1927
FT /note="Charge relay system; for 3C-like serine proteinase
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00826"
FT ACT_SITE 3714
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT ACT_SITE 3729
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT ACT_SITE 3758
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01303"
FT BINDING 3151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT BINDING 3154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT BINDING 3164
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT BINDING 3169
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT BINDING 3172
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT BINDING 3174
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT BINDING 3176
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT BINDING 3178
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT BINDING 3185
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT BINDING 3187
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT BINDING 3194
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT BINDING 3197
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00985"
FT BINDING 3293..3300
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT SITE 180..181
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:Q9WJB2"
FT SITE 383..384
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT SITE 1579..1580
FT /note="Cleavage; by CP2"
FT /evidence="ECO:0000250|UniProtKB:A0MD28"
FT SITE 1809..1810
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250|UniProtKB:A0MD28"
FT SITE 2013..2014
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250|UniProtKB:A0MD28"
FT SITE 2183..2184
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250|UniProtKB:A0MD28"
FT SITE 2199..2200
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250|UniProtKB:A0MD28"
FT SITE 2348..2349
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250|UniProtKB:A0MD28"
FT SITE 2458..2459
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250|UniProtKB:A0MD28"
FT SITE 2503..2504
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250|UniProtKB:A0MD28"
FT SITE 3144..3145
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250|UniProtKB:A0MD28"
FT SITE 3585..3586
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
FT SITE 3808..3809
FT /note="Cleavage; by 3CLSP"
FT /evidence="ECO:0000250"
FT VAR_SEQ 2504..3961
FT /note="Missing (in isoform Replicase polyprotein 1a)"
FT /evidence="ECO:0000305"
FT /id="VSP_032891"
SQ SEQUENCE 3961 AA; 433077 MW; 45D39828CC48EA77 CRC64;
MSGILDRCTC TPNARVFVAE GQVYCTRCLS ARSLLPLNLQ VPELGVLGLF YRPEEPLRWT
LPRAFPTVEC SPTGACWLSA IFPIARMTSG NLNFQQRMVR VAGEIYRAGQ LTPTVLKTIQ
VYERGCRWYP IVGPVPGVGV YANSLHVSDK PFPGATHVLT NLPLPQRPKP EDFCPFECAM
ADVYDIGRGA VMYVAGGKVS WAPRGGDEVK FEPVPKELKL VANRLHTSFP PHHVVDMSKF
TFMTPGSGVS MRVEYQYGCL PADTVPEGNC WWRLFDLLPP EVQNKEIRHA NQFGYQTKHG
VPGKYLQRRL QVNGLRAVTD THGPIVIQYF SVKESWIRHL KPVEEPSLPG FEDLLRIRVE
PNTSPLAGKN EKIFRFGSHK WYGAGKRARK ARSGATTMVA HRASSAHETR QATKHEGAGA
NKAEHLKLYS PPAEGNCGWH CISAIVNRMV NSNFETTLPE RVRPPDDWAT DEDLVNTIQI
LRLPAALDRN GACGGAKYVL KLEGEHWTVS VNPGMSPSLL PLECVQGCCE HKGGLGSPDA
VEVSGFDPAC LDRLLQVMHL PSSTIPAALA ELSDDSNRPV SPAAATWTVS QSYARHRGGN
HHDQVCLGKI ISLCQVIEDC CCHQNKTNRA TPEEVAAKID QYLRGATSLE ECLAKLERVS
PPGAADTSFD WNVVLPGVEA AHQTTEQLHV NPCRTLVPPV TQEPLGKDSV PLTAFSLSNC
YYPAQGNEVR HRERLNSVLS KLEEVVLEEY GLMSTGLGPR PVLPSGLDEL KDQMEEDLLK
LANTQATSEM MAWAAEQVDL KAWVKSYPRW TPPPPPPRVQ PRKTKSVKSL PEDKPVPAPR
RKVRSGCGSP VLMGDNVPNG SEDLTVGGPL NFPTPSEPMT PMSEPVLTPA LQRVPKLMTP
LDGSAPVPAP RRTVSRPMTP LSEPIFLSAP RHKFQQVEEA NPATTTLTHQ NEPLDLSASS
QTEYEASPLA SSQNMSILEA GGQEAEEVLS EISDILNDTS PAPVSSSSSL SSVKITRPKY
SAQAIIDSGG PCSGHLQKEK EACLSIMREA CDASKLSDPA TQEWLSRMWD RVDMLTWRNT
SAYQAFRTLN GRFEFLPKMI LETPPPHPCG FVMLPHTPAP SVSAESDLTI GSVATEDVPR
ILGKIGDTGE LLNQGPSAPF KGGPVCDQPA KNSRMSPRES DESIIAPPAD TGGAGSFTDL
PSSDSVDANG GGPLRTVKTK AGRLLDQLSC QVFSLVSHLP VFFSHLFKSD SGYSPGDWGF
AAFTLFCLFL CYSYPFFGFA PLLGVFSGSS RRVRMGVFGC WLAFAVGLFK PVSDPVGTAC
EFDSPECRNV LHSFELLKPW DPVRSLVVGP VGLGLAILGR LLGGARYVWH FLLRFGIVAD
CILAGAYVLS QGRCKKCWGS CVRTAPNEIA FNVFPFTRAT RSSLIDLCDR FCAPKGMDPI
FLATVWRGCW TGRSPIEQPS EKPIAFAQLD EKRITARTVV AQPYDPNQAV KCLRVLQAGG
AMVAEAVPKV VKVSAIPFRA PFFPAGVKVD PECRIVVDPD TFTTALRSGY STTNLVLGMG
DFAQLNGLKI RQISKPSGGG SHLVAALHVA CSMALHMLAG VYVTAVGSCG TGTNDPWCTN
PFAAPGYGPG SLCTSRLCIS QHGLTLPLTA LVAGFGLQEI ALVVLIFVSM GGMAHRLSCK
ADMLCILLAI ASYVWVPLTW LLCVFPCWLR WFSLHPLTIL WLVFFLISVN IPSGILAVVL
LVSLWLLGRY TNIAGLVTPY DIHHYTSGPR GVAALATAPD GTYLAAVRRA ALTGRTMLFT
PSQLGSLLEG AFRTQKPSLN TVNVVGSSMG SGGVFTIDGK IKCVTAAHVL TGNSARVSGV
GFNQMLDFDV KGDFAIADCP NWQGAAPKAQ FCEDGWTGRA YWLTSSGVEP GVIGNGFAFC
FTACGDSGSP VITEAGELVG VHTGSNKQGG GIVTRPSGQF CNVTPIKLSE LSEFFAGPKV
PLGDVKIGSH IIKDTCEVPS DLCALLAAKP ELEGGLSTVQ LLCVFFLLWR MMGHAWTPLV
AVGFFILNEI LPAVLVRSVF SFGMFVLSWL TPWSAQVLMI RLLTAALNRN RLSLGFYSLG
AVTSFVADLA VTQGHPLQVV MNLSTYAFLP RMMVVTSPVP VIACGVVHLL AIILYLFKYR
CLHYVLVGDG VFSSAFFLRY FAEGKLREGV SQSCGMSHES LTGALAMRLT DEDLDFLTKW
TDFKCFVSAS NMRNAAGQFI EAAYAKALRI ELAQLVQVDK VRGTLAKLEA FADTVAPQLS
PGDIVVALGH TPVGSIFDLK VGSTKHTLQA IETRVLAGSK MTVARVVDPT PAPPPVPVPI
PLPPKVLENG PNAWGDEDRL NKKKRRRMEA VGIFVMDGKK YQKFWDKNSG DVFYEEVHNS
TDEWECLRAG DPADFDPETG VQCGHITIED RVYNVFTSPS GRKFLVPANP ENRRAQWEAA
KLSVEQALGM MNVDGELTAK ELEKLKGIID KLQGLTKEQC LNCLLAASGL TRCGRGGLVV
TETAVKIVKF HNRTFTLGPV NLKVASEVEL KDAVEHNQHP VARPVDGGVV LLRSAVPSLI
DVLISGADAS PKLLARHGPG NTGIDGTLWD FEAEATKEEV ALSAQIIQAC DIRRGDAPEI
GLPYKLYPVR GNPERVKGVL QNTRFGDIPY KTPSDTGSPV HAAACLTPNA TPVTDGRSVL
ATTMPSGFEL YVPTIPASVL DYLDSRPDCP KQLTEHGCED AALRDLSKYD LVTQGFVLPG
VLRLVRKYLF AHVGKCPPVH RPSTYPAKNS MAGINGNRFP TKDIQSVPEI DVLCAQAVRE
NWQTVTPCTL KKQYCGKKKT RTILGTNNFI ALAHRAALSG VTQGFMKKAF NSPIALGKNK
FKELQTPVLG RCLEADLASC DRSTPAIVRW FAANLLYELA CAEEHLPSYV LNCCHDLLVT
QSGAVTKRGG LSSGDPITSV SNTIYSLVIY AQHMVLSYFK SGHPHGLLFL QDQLKFEDML
KVQPLIVYSD DLVLYAESPS MPNYHWWVEH LNLMLGFQTD PKKTAITDSP TFLGCRIING
RQLVPNRDRI LAALAYHMKA SNVSEYYASA AAILMDSCAC LEYDPEWFEE LVVGIAQCAR
KDGYSFPGPP FFLSMWEKLR SNHEGKKSRM CGYCMAPAPY ATACGLDVCV YHTHFHQHCP
VIIWCGHPAG SGSCGECEPP LGKGTSPLDE VLEQVPYKPP RTVIMHVEQG LTPLDPGRYQ
TRRGLVSVRR GIRGNEVDLP DGDYASTALL PTCKEINMVA VAPNVLRSRF IIGPPGAGKT
HWLLQQVQDG DVIYTPTHQT MLDMIRALGT CRFNVPAGTT LQFPAPSRTG PWVRILAGGW
CPGKNSFLDE AAYCNHLDVL RLLSKTTLTC LGDFKQLHPV GFDSHCYVFD IMPQTQLKTI
WRFGQNICDA IQPDYRDKLV SMVNTTRVTY VEKPVRYGQV LTPYHRDRED GAITIDSSQG
ATFDVVTLHL PTKDSLNRQR ALVAITRARH AIFVYDPHRQ LQSMFDLPAK GTPVNLAVHR
DEQLIVLDRN NKEITVAQAL GNGDKFRATD KRVVDSLRAI CADLEGSSSP LPKVAHNLGF
YFSPDLTQFA KLPAELAPHW PVVTTQNNER WPDRLVASLR PIHKYSRACI GAGYMVGPSV
FLGTPGVVSY YLTKFVRGEA QVLPETVFST GRIEVDCREY LDDREREVAE SLPHAFIGDV
KGTTVGGCHH VTSKYLPRFL PKESVAVVGV SSPGEAAKAF CTLTDVYLPD LEAYLHPETQ
SKCWKVMLDF KEVRLMVWKG KTAYFQLEGR HFTWYQLASY TSYIRVPVNS TVYLDPCMGP
ALCNRRVVGS THWGADLAVT PYDYGAKIIL SSAYHGEMPP GYKILACAEF SLDDPVRYKH
TWGFESDTAY LYEFTGNGED WEDYNGAFRA RQKGKIYKAT ATSMKFHFPP GPVIEPTLGL
N
//
