POLG_HE71B
ID POLG_HE71B Reviewed; 2193 AA.
AC Q66478;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Genome polyprotein;
DE Contains:
DE RecName: Full=P1;
DE Contains:
DE RecName: Full=Capsid protein VP0;
DE AltName: Full=VP4-VP2;
DE Contains:
DE RecName: Full=Capsid protein VP4;
DE AltName: Full=P1A;
DE AltName: Full=Virion protein 4;
DE Contains:
DE RecName: Full=Capsid protein VP2;
DE AltName: Full=P1B;
DE AltName: Full=Virion protein 2;
DE Contains:
DE RecName: Full=Capsid protein VP3;
DE AltName: Full=P1C;
DE AltName: Full=Virion protein 3;
DE Contains:
DE RecName: Full=Capsid protein VP1;
DE AltName: Full=P1D;
DE AltName: Full=Virion protein 1;
DE Contains:
DE RecName: Full=P2;
DE Contains:
DE RecName: Full=Protease 2A;
DE Short=P2A;
DE EC=3.4.22.29 {ECO:0000250|UniProtKB:P03300};
DE AltName: Full=Picornain 2A;
DE AltName: Full=Protein 2A;
DE Contains:
DE RecName: Full=Protein 2B;
DE Short=P2B;
DE Contains:
DE RecName: Full=Protein 2C;
DE Short=P2C;
DE EC=3.6.1.15 {ECO:0000250|UniProtKB:P03300};
DE Contains:
DE RecName: Full=P3;
DE Contains:
DE RecName: Full=Protein 3AB;
DE Contains:
DE RecName: Full=Protein 3A;
DE Short=P3A;
DE Contains:
DE RecName: Full=Viral protein genome-linked;
DE Short=VPg;
DE AltName: Full=Protein 3B;
DE Short=P3B;
DE Contains:
DE RecName: Full=Protein 3CD;
DE EC=3.4.22.28;
DE Contains:
DE RecName: Full=Protease 3C {ECO:0000255|PROSITE-ProRule:PRU01222};
DE EC=3.4.22.28 {ECO:0000255|PROSITE-ProRule:PRU01222};
DE AltName: Full=Picornain 3C {ECO:0000255|PROSITE-ProRule:PRU01222};
DE Short=P3C {ECO:0000255|PROSITE-ProRule:PRU01222};
DE Contains:
DE RecName: Full=RNA-directed RNA polymerase {ECO:0000255|PROSITE-ProRule:PRU00539};
DE Short=RdRp;
DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
DE AltName: Full=3D polymerase;
DE Short=3Dpol;
DE AltName: Full=Protein 3D;
DE Short=3D;
OS Human enterovirus 71 (strain USA/BrCr/1970) (EV71) (EV-71).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Picornavirales; Picornaviridae; Enterovirus; Enterovirus A.
OX NCBI_TaxID=69153;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=8837884; DOI=10.1016/0168-1702(95)00087-9;
RA Brown B.A., Pallansch M.A.;
RT "Complete nucleotide sequence of enterovirus 71 is distinct from
RT poliovirus.";
RL Virus Res. 39:195-206(1995).
RN [2]
RP INTERACTION WITH HOST RTN3 (PROTEIN 2C), AND MUTAGENESIS OF ASP-1121;
RP LYS-1127; GLU-1130; LYS-1135 AND ILE-1136.
RX PubMed=17182608; DOI=10.1074/jbc.m611145200;
RA Tang W.-F., Yang S.-Y., Wu B.-W., Jheng J.-R., Chen Y.-L., Shih C.-H.,
RA Lin K.-H., Lai H.-C., Tang P., Horng J.-T.;
RT "Reticulon 3 binds the 2C protein of enterovirus 71 and is required for
RT viral replication.";
RL J. Biol. Chem. 282:5888-5898(2007).
RN [3]
RP INTERACTION WITH HOST DDX58 (PROTEASE 3C), AND MUTAGENESIS OF HIS-1588;
RP ARG-1632 AND VAL-1702.
RX PubMed=20519382; DOI=10.1128/jvi.02491-09;
RA Lei X., Liu X., Ma Y., Sun Z., Yang Y., Jin Q., He B., Wang J.;
RT "The 3C protein of enterovirus 71 inhibits retinoid acid-inducible gene I-
RT mediated interferon regulatory factor 3 activation and type I interferon
RT responses.";
RL J. Virol. 84:8051-8061(2010).
RN [4]
RP FUNCTION (PROTEASE 3C), AND MUTAGENESIS OF HIS-1588; ARG-1632 AND VAL-1702.
RX PubMed=23175366; DOI=10.1128/jvi.01855-12;
RA Lei X., Xiao X., Xue Q., Jin Q., He B., Wang J.;
RT "Cleavage of interferon regulatory factor 7 by enterovirus 71 3C suppresses
RT cellular responses.";
RL J. Virol. 87:1690-1698(2013).
RN [5]
RP FUNCTION (CAPSID PROTEIN VP1).
RC STRAIN=H;
RX PubMed=20956521; DOI=10.1074/jbc.m110.168468;
RA Hussain K.M., Leong K.L., Ng M.M., Chu J.J.;
RT "The essential role of clathrin-mediated endocytosis in the infectious
RT entry of human enterovirus 71.";
RL J. Biol. Chem. 286:309-321(2011).
RN [6]
RP FUNCTION (PROTEASE 2A), AND FUNCTION (PROTEASE 3C).
RX PubMed=24390337; DOI=10.1128/jvi.02712-13;
RA Feng Q., Langereis M.A., Lork M., Nguyen M., Hato S.V., Lanke K., Emdad L.,
RA Bhoopathi P., Fisher P.B., Lloyd R.E., van Kuppeveld F.J.;
RT "Enterovirus 2Apro targets MDA5 and MAVS in infected cells.";
RL J. Virol. 88:3369-3378(2014).
RN [7]
RP FUNCTION (PROTEIN 2B), INTERACTION WITH HOST BAX (PROTEIN 2B), AND
RP SUBCELLULAR LOCATION (PROTEIN 2B).
RX PubMed=27558414; DOI=10.1128/jvi.01499-16;
RA Cong H., Du N., Yang Y., Song L., Zhang W., Tien P.;
RT "Enterovirus 71 2B induces cell apoptosis by directly inducing the
RT conformational activation of the proapoptotic protein Bax.";
RL J. Virol. 90:9862-9877(2016).
RN [8]
RP FUNCTION (PROTEASE 2A), AND MUTAGENESIS OF CYS-972.
RC STRAIN=Fuyang-0805;
RX PubMed=28253362; DOI=10.1371/journal.ppat.1006243;
RA Wang B., Xi X., Lei X., Zhang X., Cui S., Wang J., Jin Q., Zhao Z.;
RT "Correction: Enterovirus 71 Protease 2Apro Targets MAVS to Inhibit Anti-
RT Viral Type I Interferon Responses.";
RL PLoS Pathog. 13:E1006243-E1006243(2017).
RN [9]
RP FUNCTION (PROTEIN RNA-DIRECTED RNA POLYMERASE), INTERACTION WITH HOST NLRP3
RP (PROTEIN RNA-DIRECTED RNA POLYMERASE), AND SUBCELLULAR LOCATION (PROTEIN
RP RNA-DIRECTED RNA POLYMERASE).
RX PubMed=28060938; DOI=10.1371/journal.ppat.1006123;
RA Wang W., Xiao F., Wan P., Pan P., Zhang Y., Liu F., Wu K., Liu Y., Wu J.;
RT "EV71 3D Protein Binds with NLRP3 and Enhances the Assembly of Inflammasome
RT Complex.";
RL PLoS Pathog. 13:e1006123-e1006123(2017).
RN [10]
RP FUNCTION (PROTEASE 3C), SUBCELLULAR LOCATION (PROTEASE 3C), AND MUTAGENESIS
RP OF CYS-1695.
RX PubMed=27847364; DOI=10.1128/jvi.02016-16;
RA Li J., Yao Y., Chen Y., Xu X., Lin Y., Yang Z., Qiao W., Tan J.;
RT "Enterovirus 71 3C Promotes Apoptosis through Cleavage of PinX1, a Telomere
RT Binding Protein.";
RL J. Virol. 91:0-0(2017).
RN [11]
RP FUNCTION (PROTEASE 3C), SUBCELLULAR LOCATION (PROTEASE 3C), SUBCELLULAR
RP LOCATION (CAPSID PROTEIN VP0), SUBCELLULAR LOCATION (CAPSID PROTEIN VP4),
RP SUBCELLULAR LOCATION (CAPSID PROTEIN VP3), SUBCELLULAR LOCATION (CAPSID
RP PROTEIN VP2), SUBCELLULAR LOCATION (CAPSID PROTEIN VP1), SUBCELLULAR
RP LOCATION (PROTEASE 2A), SUBCELLULAR LOCATION (PROTEIN 2B), SUBCELLULAR
RP LOCATION (PROTEIN 2C), SUBCELLULAR LOCATION (PROTEIN 3A), SUBCELLULAR
RP LOCATION (VIRAL PROTEIN GENOME-LINKED), AND SUBCELLULAR LOCATION
RP (RNA-DIRECTED RNA POLYMERASE).
RX PubMed=30006004; DOI=10.1016/j.virusres.2018.07.006;
RA Zhang Y., Yao L., Xu X., Han H., Li P., Zou D., Li X., Zheng L., Cheng L.,
RA Shen Y., Wang X., Wu X., Xu J., Song B., Xu S., Zhang H., Cao H.;
RT "Enterovirus 71 inhibits cytoplasmic stress granule formation during the
RT late stage of infection.";
RL Virus Res. 255:55-67(2018).
RN [12]
RP FUNCTION (PROTEIN 3A).
RX PubMed=30755512; DOI=10.1128/mbio.02742-18;
RA Lyoo H., van der Schaar H.M., Dorobantu C.M., Rabouw H.H.,
RA Strating J.R.P.M., van Kuppeveld F.J.M.;
RT "ACBD3 is an essential pan-enterovirus host factor that mediates the
RT interaction between viral 3A protein and cellular protein PI4KB.";
RL MBio 10:0-0(2019).
RN [13]
RP PROTEOLYTIC CLEAVAGE (GENOME POLYPROTEIN), AND MUTAGENESIS OF LYS-69;
RP 69-LYS-SER-70 AND SER-70.
RC STRAIN=BJ97;
RX PubMed=31195113; DOI=10.1016/j.micpath.2019.103568;
RA Cao J., Liu H., Qu M., Hou A., Zhou Y., Sun B., Cai L., Gao F., Su W.,
RA Jiang C.;
RT "Determination of the cleavage site of enterovirus 71 VP0 and the effect of
RT this cleavage on viral infectivity and assembly.";
RL Microb. Pathog. 134:103568-103568(2019).
RN [14]
RP FUNCTION (PROTEASE 3C).
RC STRAIN=TW/2231/98;
RX PubMed=31498791; DOI=10.1371/journal.pone.0221048;
RA Li M.L., Lin J.Y., Chen B.S., Weng K.F., Shih S.R., Calderon J.D.,
RA Tolbert B.S., Brewer G.;
RT "EV71 3C protease induces apoptosis by cleavage of hnRNP A1 to promote
RT apaf-1 translation.";
RL PLoS ONE 14:E0221048-E0221048(2019).
RN [15]
RP FUNCTION (PROTEASE 2A), AND FUNCTION (PROTEASE 3C).
RX PubMed=30867299; DOI=10.1128/jvi.00222-19;
RA Visser L.J., Langereis M.A., Rabouw H.H., Wahedi M., Muntjewerff E.M.,
RA de Groot R.J., van Kuppeveld F.J.M.;
RT "Essential Role of Enterovirus 2A Protease in Counteracting Stress Granule
RT Formation and the Induction of Type I Interferon.";
RL J. Virol. 93:0-0(2019).
RN [16]
RP INTERACTION WITH HUMAN PROTEIN ILF2 (PROTEIN 2B).
RX PubMed=31212927; DOI=10.3390/v11060559;
RA Cui X., Qian P., Rao T., Wei Y., Zhao F., Zhang H., Chen H., Li X.;
RT "Cellular Interleukin Enhancer-Binding Factor 2, ILF2, Inhibits Japanese
RT Encephalitis Virus Replication In Vitro.";
RL Viruses 11:0-0(2019).
RN [17]
RP FUNCTION (PROTEASE 3C), SUBCELLULAR LOCATION (PROTEASE 3C), AND MUTAGENESIS
RP OF VAL-1702.
RX PubMed=34930370; DOI=10.1186/s12985-021-01725-7;
RA Li Z., Wu Y., Li H., Li W., Tan J., Qiao W.;
RT "3C protease of enterovirus 71 cleaves promyelocytic leukemia protein and
RT impairs PML-NBs production.";
RL Virol. J. 18:255-255(2021).
RN [18]
RP FUNCTION (PROTEIN 3CD), INTERACTION WITH HOST PPP1R15A (PROTEIN 3CD),
RP SUBCELLULAR LOCATION (PROTEIN 3CD), AND MUTAGENESIS OF TYR-1989.
RX PubMed=34985336; DOI=10.1128/spectrum.01388-21;
RA Li H., Li W., Zhang S., Qiu M., Li Z., Lin Y., Tan J., Qiao W.;
RT "Enterovirus 71 Activates GADD34 via Precursor 3CD to Promote IRES-Mediated
RT Viral Translation.";
RL Microbiol. Spectr. 0:0-0(2022).
CC -!- FUNCTION: [Capsid protein VP1]: Forms an icosahedral capsid of pseudo
CC T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The
CC capsid is 300 Angstroms in diameter, composed of 60 copies of each
CC capsid protein and enclosing the viral positive strand RNA genome (By
CC similarity). Capsid protein VP1 mainly forms the vertices of the capsid
CC (By similarity). Capsid protein VP1, together with VP2, interacts with
CC host cell receptor SCARB2 to provide virion attachment to target host
CC cells. This attachment induces virion internalization predominantly
CC through clathrin-dependent endocytosis (PubMed:20956521). After binding
CC to its receptor, the capsid undergoes conformational changes (By
CC similarity). Capsid protein VP1 N-terminus (that contains an
CC amphipathic alpha-helix) and capsid protein VP4 are externalized (By
CC similarity). Together, they shape a pore in the host membrane through
CC which viral genome is translocated to host cell cytoplasm (By
CC similarity). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000269|PubMed:20956521}.
CC -!- FUNCTION: [Capsid protein VP2]: Forms an icosahedral capsid of pseudo
CC T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The
CC capsid is 300 Angstroms in diameter, composed of 60 copies of each
CC capsid protein and enclosing the viral positive strand RNA genome (By
CC similarity). Capsid protein VP2, together with VP1, interacts with host
CC cell receptor SCARB2 to provide virion attachment to target host cells
CC (By similarity). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000250|UniProtKB:Q66479}.
CC -!- FUNCTION: [Capsid protein VP3]: Forms an icosahedral capsid of pseudo
CC T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The
CC capsid is 300 Angstroms in diameter, composed of 60 copies of each
CC capsid protein and enclosing the viral positive strand RNA genome (By
CC similarity). {ECO:0000250|UniProtKB:P03300}.
CC -!- FUNCTION: [Capsid protein VP4]: Lies on the inner surface of the capsid
CC shell (By similarity). After binding to the host receptor, the capsid
CC undergoes conformational changes (By similarity). Capsid protein VP4 is
CC released, Capsid protein VP1 N-terminus is externalized, and together,
CC they shape a pore in the host membrane through which the viral genome
CC is translocated into the host cell cytoplasm (By similarity).
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- FUNCTION: [Capsid protein VP0]: Component of immature procapsids, which
CC is cleaved into capsid proteins VP4 and VP2 after maturation (By
CC similarity). Allows the capsid to remain inactive before the maturation
CC step (By similarity). {ECO:0000250|UniProtKB:P03300}.
CC -!- FUNCTION: [Protease 2A]: Cysteine protease that cleaves viral
CC polyprotein and specific host proteins (By similarity). It is
CC responsible for the autocatalytic cleavage between the P1 and P2
CC regions, which is the first cleavage occurring in the polyprotein (By
CC similarity). Cleaves also the host translation initiation factor
CC EIF4G1, in order to shut down the capped cellular mRNA translation (By
CC similarity). Inhibits the host nucleus-cytoplasm protein and RNA
CC trafficking by cleaving host members of the nuclear pores (By
CC similarity). Counteracts stress granule formation probably by
CC antagonizing its assembly or promoting its dissassembly
CC (PubMed:30867299). Cleaves and inhibits host IFIH1/MDA5, thereby
CC inhibiting the type-I IFN production and the establishment of the
CC antiviral state (PubMed:24390337). Cleaves and inhibits host MAVS,
CC thereby inhibiting the type-I IFN production and the establishment of
CC the antiviral state (PubMed:24390337, PubMed:28253362).
CC {ECO:0000250|UniProtKB:P03300, ECO:0000269|PubMed:24390337,
CC ECO:0000269|PubMed:28253362, ECO:0000269|PubMed:30867299}.
CC -!- FUNCTION: [Protein 2B]: Plays an essential role in the virus
CC replication cycle by acting as a viroporin. Creates a pore in the host
CC reticulum endoplasmic and as a consequence releases Ca2+ in the
CC cytoplasm of infected cell (By similarity). In turn, high levels of
CC cytoplasmic calcium may trigger membrane trafficking and transport of
CC viral ER-associated proteins to viroplasms, sites of viral genome
CC replication (By similarity). Activates also the mitochondrial apoptotic
CC pathway by activating host BAX (PubMed:27558414).
CC {ECO:0000250|UniProtKB:P03300, ECO:0000269|PubMed:27558414}.
CC -!- FUNCTION: [Protein 2C]: Induces and associates with structural
CC rearrangements of intracellular membranes. Displays RNA-binding,
CC nucleotide binding and NTPase activities. May play a role in virion
CC morphogenesis and viral RNA encapsidation by interacting with the
CC capsid protein VP3. {ECO:0000250|UniProtKB:P03300}.
CC -!- FUNCTION: [Protein 3AB]: Localizes the viral replication complex to the
CC surface of membranous vesicles. Together with protein 3CD binds the
CC Cis-Active RNA Element (CRE) which is involved in RNA synthesis
CC initiation. Acts as a cofactor to stimulate the activity of 3D
CC polymerase, maybe through a nucleid acid chaperone activity.
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- FUNCTION: [Protein 3A]: Localizes the viral replication complex to the
CC surface of membranous vesicles (By similarity). It inhibits host cell
CC endoplasmic reticulum-to-Golgi apparatus transport and causes the
CC disassembly of the Golgi complex, possibly through GBF1 interaction (By
CC similarity). This would result in depletion of MHC, trail receptors and
CC IFN receptors at the host cell surface (By similarity). Plays an
CC essential role in viral RNA replication by recruiting ACBD3 and PI4KB
CC at the viral replication sites, thereby allowing the formation of the
CC rearranged membranous structures where viral replication takes place
CC (Probable). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000305|PubMed:30755512}.
CC -!- FUNCTION: [Viral protein genome-linked]: Acts as a primer for viral RNA
CC replication and remains covalently bound to viral genomic RNA. VPg is
CC uridylylated prior to priming replication into VPg-pUpU (By
CC similarity). The oriI viral genomic sequence may act as a template for
CC this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by
CC the RNA-dependent RNA polymerase to replicate the viral genome (By
CC similarity). Following genome release from the infecting virion in the
CC cytoplasm, the VPg-RNA linkage is probably removed by host TDP2 (By
CC similarity). During the late stage of the replication cycle, host TDP2
CC is excluded from sites of viral RNA synthesis and encapsidation,
CC allowing for the generation of progeny virions (By similarity).
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- FUNCTION: [Protein 3CD]: Involved in the viral replication complex and
CC viral polypeptide maturation. It exhibits protease activity with a
CC specificity and catalytic efficiency that is different from protease
CC 3C. Protein 3CD lacks polymerase activity. Protein 3CD binds to the
CC 5'UTR of the viral genome. Regulates host protein expression by
CC interacting with host PPP1R15A to support viral replication
CC (PubMed:34985336). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000269|PubMed:34985336}.
CC -!- FUNCTION: [Protease 3C]: Major viral protease that mediates proteolytic
CC processing of the polyprotein (By similarity). Cleaves host EIF5B,
CC contributing to host translation shutoff (By similarity). Cleaves also
CC host PABPC1, contributing to host translation shutoff (By similarity).
CC Disassembles host cytoplasmic stress granules by cleaving host G3BP1,
CC although this effect is less prononced than the inhibition induced by
CC protease 2A (PubMed:30006004, PubMed:30867299). Cleaves host DDX58/RIG-
CC I and thus contributes to the inhibition of type I interferon
CC production (PubMed:24390337). Cleaves host IRF7 and thus contributes to
CC the inhibition of type I interferon production (PubMed:23175366).
CC Cleaves host HNRNPA1 thereby increasing the translation of apoptosis
CC protease activating factor APAF1, leading to apoptosis of the host cell
CC (PubMed:31498791). Cleaves host NLRP1, triggers host N-glycine-mediated
CC degradation of the autoinhibitory NLRP1 N-terminal fragment (By
CC similarity). Promotes also apoptosis in infected cell through cleaving
CC of host PINX1, a telomere binding protein in order to facilitate viral
CC release (PubMed:27847364). Impairs host PML-NBs production via PML
CC cleavage and counter its antiviral activities (PubMed:34930370).
CC {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03303,
CC ECO:0000269|PubMed:23175366, ECO:0000269|PubMed:24390337,
CC ECO:0000269|PubMed:27847364, ECO:0000269|PubMed:30006004,
CC ECO:0000269|PubMed:30867299, ECO:0000269|PubMed:31498791,
CC ECO:0000269|PubMed:34930370}.
CC -!- FUNCTION: [RNA-directed RNA polymerase]: Replicates the viral genomic
CC RNA on the surface of intracellular membranes. May form linear arrays
CC of subunits that propagate along a strong head-to-tail interaction
CC called interface-I. Covalently attaches UMP to a tyrosine of VPg, which
CC is used to prime RNA synthesis. The positive stranded RNA genome is
CC first replicated at virus induced membranous vesicles, creating a dsRNA
CC genomic replication form. This dsRNA is then used as template to
CC synthesize positive stranded RNA genomes. ss(+)RNA genomes are either
CC translated, replicated or encapsidated. Facilitates the assembly of
CC NLRP3 inflammasome complex and stimulates the cleavage of host pro-
CC CASP1 and the secretion of IL-1beta (PubMed:28060938).
CC {ECO:0000250|UniProtKB:P03300, ECO:0000269|PubMed:28060938}.
CC -!- CATALYTIC ACTIVITY: [Protein 2C]:
CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
CC Evidence={ECO:0000250|UniProtKB:P03300};
CC -!- CATALYTIC ACTIVITY: [Protease 2A]:
CC Reaction=Selective cleavage of Tyr-|-Gly bond in the picornavirus
CC polyprotein.; EC=3.4.22.29; Evidence={ECO:0000250|UniProtKB:P03300};
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: [Protease 3C]:
CC Reaction=Selective cleavage of Gln-|-Gly bond in the poliovirus
CC polyprotein. In other picornavirus reactions Glu may be substituted
CC for Gln, and Ser or Thr for Gly.; EC=3.4.22.28;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01222};
CC -!- COFACTOR: [RNA-directed RNA polymerase]:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P03300};
CC Note=Binds 2 magnesium ions that constitute a dinuclear catalytic metal
CC center (By similarity). The magnesium ions are not prebound but only
CC present for catalysis (By similarity). Requires the presence of 3CDpro
CC or 3CPro (By similarity). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000250|UniProtKB:P03313};
CC -!- ACTIVITY REGULATION: [RNA-directed RNA polymerase]: Replication or
CC transcription is subject to high level of random mutations by the
CC nucleotide analog ribavirin. {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [Capsid protein VP0]: Interacts with capsid protein VP1 and
CC capsid protein VP3 to form heterotrimeric protomers.
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [Capsid protein VP1]: Interacts with capsid protein VP0, and
CC capsid protein VP3 to form heterotrimeric protomers (By similarity).
CC Five protomers subsequently associate to form pentamers which serve as
CC building blocks for the capsid (By similarity). Interacts with capsid
CC protein VP2, capsid protein VP3 and capsid protein VP4 following
CC cleavage of capsid protein VP0 (By similarity). Interacts with host
CC SCARB2 (By similarity). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000250|UniProtKB:Q66479}.
CC -!- SUBUNIT: [Capsid protein VP2]: Interacts with capsid protein VP1 and
CC capsid protein VP3 in the mature capsid (By similarity). Interacts with
CC host SCARB2 (By similarity). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000250|UniProtKB:Q66479}.
CC -!- SUBUNIT: [Capsid protein VP3]: Interacts with capsid protein VP0 and
CC capsid protein VP1 to form heterotrimeric protomers (By similarity).
CC Five protomers subsequently associate to form pentamers which serve as
CC building blocks for the capsid (By similarity). Interacts with capsid
CC protein VP4 in the mature capsid (By similarity). Interacts with
CC protein 2C; this interaction may be important for virion morphogenesis
CC (By similarity). {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [Capsid protein VP4]: Interacts with capsid protein VP1 and
CC capsid protein VP3. {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [Protease 2A]: Homodimer. {ECO:0000250|UniProtKB:Q9QF31}.
CC -!- SUBUNIT: [Protein 2B]: Interacts with host BAX; this interaction
CC activates the mitochondrial apoptotic pathway. Interacts with host ILF2
CC (PubMed:31212927). {ECO:0000269|PubMed:27558414,
CC ECO:0000269|PubMed:31212927}.
CC -!- SUBUNIT: [Protein 2C]: Homohexamer; forms a hexameric ring structure
CC with 6-fold symmetry characteristic of AAA+ ATPases (By similarity).
CC Interacts (via N-terminus) with host RTN3 (via reticulon domain); this
CC interaction is important for viral replication (PubMed:17182608).
CC Interacts with capsid protein VP3; this interaction may be important
CC for virion morphogenesis (By similarity).
CC {ECO:0000250|UniProtKB:P03300, ECO:0000269|PubMed:17182608}.
CC -!- SUBUNIT: [Protein 3AB]: Interacts with protein 3CD.
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [Protein 3A]: Homodimer (By similarity). Interacts with host
CC GBF1 (By similarity). Interacts (via GOLD domain) with host ACBD3 (via
CC GOLD domain); this interaction allows the formation of a viral protein
CC 3A/ACBD3 heterotetramer with a 2:2 stoichiometry, which will stimulate
CC the recruitment of host PI4KB in order to synthesize PI4P at the viral
CC RNA replication sites (By similarity). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000250|UniProtKB:Q66479}.
CC -!- SUBUNIT: [Viral protein genome-linked]: Interacts with RNA-directed RNA
CC polymerase. {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [Protease 3C]: Interacts with host IFIH1/MDA5; this
CC interaction inhibits host IFIH1 (By similarity). Interacts with host
CC DDX58 (PubMed:20519382). {ECO:0000250|UniProtKB:Q9QF31,
CC ECO:0000269|PubMed:20519382}.
CC -!- SUBUNIT: [Protein 3CD]: Interacts with protein 3AB and with RNA-
CC directed RNA polymerase. Interacts with host PPP1R15A
CC (PubMed:34985336). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000269|PubMed:34985336}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase]: Interacts with Viral protein
CC genome-linked and with protein 3CD. Interacts with host NLRP3
CC (PubMed:28060938). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000269|PubMed:28060938}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP0]: Virion. Host cytoplasm
CC {ECO:0000269|PubMed:30006004}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP4]: Virion.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP2]: Virion
CC {ECO:0000250|UniProtKB:P03300}. Host cytoplasm
CC {ECO:0000269|PubMed:30006004}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion
CC {ECO:0000250|UniProtKB:P03300}. Host cytoplasm
CC {ECO:0000269|PubMed:30006004}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion
CC {ECO:0000250|UniProtKB:P03300}. Host cytoplasm
CC {ECO:0000269|PubMed:30006004}.
CC -!- SUBCELLULAR LOCATION: [Protein 2B]: Host cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:27558414, ECO:0000269|PubMed:30006004}; Peripheral
CC membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC Note=Probably localizes to the surface of intracellular membrane
CC vesicles that are induced after virus infection as the site for viral
CC RNA replication. These vesicles are derived from the endoplasmic
CC reticulum.
CC -!- SUBCELLULAR LOCATION: [Protein 2C]: Host cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:30006004}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes
CC to the surface of intracellular membrane vesicles that are induced
CC after virus infection as the site for viral RNA replication. These
CC vesicles are derived from the endoplasmic reticulum.
CC -!- SUBCELLULAR LOCATION: [Protein 3A]: Host cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:30006004}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes
CC to the surface of intracellular membrane vesicles that are induced
CC after virus infection as the site for viral RNA replication. These
CC vesicles are derived from the endoplasmic reticulum.
CC -!- SUBCELLULAR LOCATION: [Protein 3AB]: Host cytoplasmic vesicle membrane
CC {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic
CC side {ECO:0000305}. Note=Probably localizes to the surface of
CC intracellular membrane vesicles that are induced after virus infection
CC as the site for viral RNA replication. These vesicles are derived from
CC the endoplasmic reticulum.
CC -!- SUBCELLULAR LOCATION: [Viral protein genome-linked]: Virion
CC {ECO:0000250|UniProtKB:P03300}. Host cytoplasm
CC {ECO:0000269|PubMed:30006004}.
CC -!- SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm
CC {ECO:0000269|PubMed:27847364, ECO:0000269|PubMed:30006004,
CC ECO:0000269|PubMed:34930370}. Host nucleus
CC {ECO:0000269|PubMed:34930370}.
CC -!- SUBCELLULAR LOCATION: [Protein 3CD]: Host nucleus
CC {ECO:0000250|UniProtKB:P03300}. Host cytoplasm
CC {ECO:0000269|PubMed:30006004}. Host cytoplasmic vesicle membrane
CC {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic
CC side {ECO:0000305}. Note=Probably localizes to the surface of
CC intracellular membrane vesicles that are induced after virus infection
CC as the site for viral RNA replication. These vesicles are derived from
CC the endoplasmic reticulum.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasmic
CC vesicle membrane {ECO:0000305}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Host cytoplasm
CC {ECO:0000269|PubMed:28060938}. Note=Probably localizes to the surface
CC of intracellular membrane vesicles that are induced after virus
CC infection as the site for viral RNA replication. These vesicles are
CC derived from the endoplasmic reticulum.
CC -!- DOMAIN: [Protein 2C]: The N-terminus has membrane-binding (By
CC similarity). The N-terminus also displays RNA-binding properties (By
CC similarity). The N-terminus is involved in oligomerization (By
CC similarity). The central part contains an ATPase domain and a
CC degenerate C4-type zinc-finger with only 3 cysteines (By similarity).
CC The C-terminus is involved in RNA-binding (By similarity). The extreme
CC C-terminus contains a region involved in oligomerization (By
CC similarity). {ECO:0000250|UniProtKB:B9VUU3,
CC ECO:0000250|UniProtKB:P03300}.
CC -!- PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo by the
CC viral proteases yield processing intermediates and the mature proteins.
CC {ECO:0000269|PubMed:31195113}.
CC -!- PTM: [Capsid protein VP0]: Myristoylation is required for the formation
CC of pentamers during virus assembly. Further assembly of 12 pentamers
CC and a molecule of genomic RNA generates the provirion.
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- PTM: [Capsid protein VP0]: During virion maturation, immature virions
CC are rendered infectious following cleavage of VP0 into VP4 and VP2.
CC This maturation seems to be an autocatalytic event triggered by the
CC presence of RNA in the capsid and it is followed by a conformational
CC change infectious virion. {ECO:0000250|UniProtKB:P03300}.
CC -!- PTM: [Capsid protein VP4]: Myristoylation is required during RNA
CC encapsidation and formation of the mature virus particle.
CC {ECO:0000250|UniProtKB:P03300}.
CC -!- PTM: [Viral protein genome-linked]: VPg is uridylylated by the
CC polymerase into VPg-pUpU. This acts as a nucleotide-peptide primer for
CC the genomic RNA replication. {ECO:0000250|UniProtKB:P03300}.
CC -!- SIMILARITY: Belongs to the picornaviruses polyprotein family.
CC {ECO:0000305}.
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DR EMBL; U22521; AAB39968.1; -; Genomic_RNA.
DR SMR; Q66478; -.
DR BindingDB; Q66478; -.
DR ChEMBL; CHEMBL4295606; -.
DR MEROPS; C03.014; -.
DR MEROPS; C03.020; -.
DR PRIDE; Q66478; -.
DR BRENDA; 3.4.22.29; 9653.
DR Proteomes; UP000007709; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:UniProtKB.
DR GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR GO; GO:0044385; C:integral to membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0039618; C:T=pseudo3 icosahedral viral capsid; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0005216; F:ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017111; F:nucleoside-triphosphatase activity; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003724; F:RNA helicase activity; IEA:InterPro.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0039520; P:induction by virus of host autophagy; ISS:UniProtKB.
DR GO; GO:0039526; P:modulation by virus of host apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0062030; P:negative regulation of stress granule assembly; IDA:UniProtKB.
DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO:0044694; P:pore-mediated entry of viral genome into host cell; IEA:UniProtKB-KW.
DR GO; GO:0039690; P:positive stranded viral RNA replication; ISS:UniProtKB.
DR GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0018144; P:RNA-protein covalent cross-linking; IEA:UniProtKB-KW.
DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW.
DR GO; GO:0039522; P:suppression by virus of host mRNA export from nucleus; ISS:UniProtKB.
DR GO; GO:0039611; P:suppression by virus of host translation initiation factor activity; ISS:UniProtKB.
DR GO; GO:0039554; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of host MDA-5 activity; IEA:UniProtKB-KW.
DR GO; GO:0039540; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of host RIG-I activity; IEA:UniProtKB-KW.
DR GO; GO:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR CDD; cd00205; rhv_like; 3.
DR Gene3D; 2.40.10.10; -; 4.
DR Gene3D; 2.60.120.20; -; 3.
DR Gene3D; 3.30.70.270; -; 1.
DR Gene3D; 6.10.20.20; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR000605; Helicase_SF3_ssDNA/RNA_vir.
DR InterPro; IPR014759; Helicase_SF3_ssRNA_vir.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR014838; P3A.
DR InterPro; IPR036203; P3A_soluble_dom.
DR InterPro; IPR044067; PCV_3C_PRO.
DR InterPro; IPR000081; Peptidase_C3.
DR InterPro; IPR000199; Peptidase_C3A/C3B_picornavir.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR003138; Pico_P1A.
DR InterPro; IPR002527; Pico_P2B.
DR InterPro; IPR001676; Picornavirus_capsid.
DR InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR InterPro; IPR033703; Rhv-like.
DR InterPro; IPR001205; RNA-dir_pol_C.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR InterPro; IPR029053; Viral_coat.
DR Pfam; PF08727; P3A; 1.
DR Pfam; PF00548; Peptidase_C3; 1.
DR Pfam; PF02226; Pico_P1A; 1.
DR Pfam; PF00947; Pico_P2A; 1.
DR Pfam; PF01552; Pico_P2B; 1.
DR Pfam; PF00680; RdRP_1; 1.
DR Pfam; PF00073; Rhv; 3.
DR Pfam; PF00910; RNA_helicase; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF50494; SSF50494; 2.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR SUPFAM; SSF89043; SSF89043; 1.
DR PROSITE; PS51874; PCV_3C_PRO; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR PROSITE; PS51218; SF3_HELICASE_2; 1.
PE 1: Evidence at protein level;
KW Activation of host autophagy by virus; ATP-binding; Autocatalytic cleavage;
KW Capsid protein; Clathrin-mediated endocytosis of virus by host;
KW Covalent protein-RNA linkage; DNA replication;
KW Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host translation shutoff by virus; Helicase; Host cytoplasm;
KW Host cytoplasmic vesicle; Host gene expression shutoff by virus;
KW Host membrane; Host mRNA suppression by virus; Host nucleus;
KW Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host MAVS by virus; Inhibition of host MDA5 by virus;
KW Inhibition of host mRNA nuclear export by virus;
KW Inhibition of host RIG-I by virus; Inhibition of host RLR pathway by virus;
KW Ion channel; Ion transport; Lipoprotein; Magnesium; Membrane;
KW Metal-binding; Modulation of host cell apoptosis by virus; Myristate;
KW Nucleotide-binding; Nucleotidyltransferase; Phosphoprotein;
KW Pore-mediated penetration of viral genome into host cell; Protease; Repeat;
KW RNA-binding; RNA-directed RNA polymerase;
KW T=pseudo3 icosahedral capsid protein; Thiol protease; Transferase;
KW Transport; Viral attachment to host cell; Viral immunoevasion;
KW Viral ion channel; Viral penetration into host cytoplasm;
KW Viral RNA replication; Virion; Virus endocytosis by host;
KW Virus entry into host cell; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed; by host"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT CHAIN 2..2193
FT /note="Genome polyprotein"
FT /id="PRO_0000426136"
FT CHAIN 2..862
FT /note="P1"
FT /id="PRO_0000426137"
FT CHAIN 2..323
FT /note="Capsid protein VP0"
FT /id="PRO_0000426138"
FT CHAIN 2..69
FT /note="Capsid protein VP4"
FT /id="PRO_0000426139"
FT CHAIN 70..323
FT /note="Capsid protein VP2"
FT /id="PRO_0000426140"
FT CHAIN 324..565
FT /note="Capsid protein VP3"
FT /id="PRO_0000426141"
FT CHAIN 566..862
FT /note="Capsid protein VP1"
FT /id="PRO_0000426142"
FT CHAIN 863..1440
FT /note="P2"
FT /id="PRO_0000426143"
FT CHAIN 863..1012
FT /note="Protease 2A"
FT /id="PRO_0000039485"
FT CHAIN 1013..1111
FT /note="Protein 2B"
FT /id="PRO_0000039486"
FT CHAIN 1112..1440
FT /note="Protein 2C"
FT /id="PRO_0000039487"
FT CHAIN 1441..2193
FT /note="P3"
FT /id="PRO_0000426144"
FT CHAIN 1441..1548
FT /note="Protein 3AB"
FT /id="PRO_0000426145"
FT CHAIN 1441..1526
FT /note="Protein 3A"
FT /id="PRO_0000039488"
FT CHAIN 1527..1548
FT /note="Viral protein genome-linked"
FT /id="PRO_0000426146"
FT CHAIN 1549..2193
FT /note="Protein 3CD"
FT /id="PRO_0000426147"
FT CHAIN 1549..1731
FT /note="Protease 3C"
FT /id="PRO_0000426148"
FT CHAIN 1732..2193
FT /note="RNA-directed RNA polymerase"
FT /id="PRO_0000426149"
FT TOPO_DOM 2..1503
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 1504..1519
FT /evidence="ECO:0000255"
FT TOPO_DOM 1520..2193
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1216..1374
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DOMAIN 1549..1727
FT /note="Peptidase C3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT DOMAIN 1958..2073
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT ZN_FING 1381..1397
FT /note="C4-type; degenerate"
FT /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 566..588
FT /note="Amphipathic alpha-helix"
FT /evidence="ECO:0000255"
FT REGION 568..588
FT /note="Amphipathic alpha-helix"
FT /evidence="ECO:0000255"
FT REGION 1112..1250
FT /note="Oligomerization"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT REGION 1112..1184
FT /note="Membrane-binding"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT REGION 1133..1137
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT REGION 1424..1431
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT REGION 1435..1440
FT /note="Oligomerization"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT ACT_SITE 883
FT /note="For protease 2A activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT ACT_SITE 901
FT /note="For protease 2A activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT ACT_SITE 972
FT /note="For protease 2A activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT ACT_SITE 1588
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT ACT_SITE 1619
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT ACT_SITE 1695
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT BINDING 918
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:Q9QF31"
FT BINDING 920
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:Q9QF31"
FT BINDING 978
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:Q9QF31"
FT BINDING 980
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:Q9QF31"
FT BINDING 1240..1247
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT BINDING 1381
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT BINDING 1392
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT BINDING 1397
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT BINDING 1964
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT BINDING 1964
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT BINDING 2060
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT BINDING 2060
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT SITE 25
FT /note="Involved in the interaction with host RTN3"
FT /evidence="ECO:0000269|PubMed:17182608"
FT SITE 69..70
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:31195113"
FT SITE 323..324
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 862..863
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1012..1013
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1111..1112
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1136
FT /note="Involved in the interaction with host RTN3"
FT /evidence="ECO:0000269|PubMed:17182608"
FT SITE 1440..1441
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1526..1527
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1548..1549
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1731..1732
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT MOD_RES 1529
FT /note="O-(5'-phospho-RNA)-tyrosine"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT LIPID 2
FT /note="N-myristoyl glycine; by host"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT MUTAGEN 69..70
FT /note="KS->FK: Lethal."
FT /evidence="ECO:0000269|PubMed:31195113"
FT MUTAGEN 69..70
FT /note="KS->TP: Lethal."
FT /evidence="ECO:0000269|PubMed:31195113"
FT MUTAGEN 69
FT /note="K->P: No effect on VP0 cleavage and viral
FT infectivity."
FT /evidence="ECO:0000269|PubMed:31195113"
FT MUTAGEN 69
FT /note="K->T: No effect on VP0 cleavage and viral
FT infectivity."
FT /evidence="ECO:0000269|PubMed:31195113"
FT MUTAGEN 70
FT /note="S->A: Lethal."
FT /evidence="ECO:0000269|PubMed:31195113"
FT MUTAGEN 70
FT /note="S->T: Lethal."
FT /evidence="ECO:0000269|PubMed:31195113"
FT MUTAGEN 972
FT /note="C->A: Complete loss of cleavage of host MAVS."
FT /evidence="ECO:0000269|PubMed:28253362"
FT MUTAGEN 1121
FT /note="D->V: No effect on the interaction with RTN3; when
FT associated with V-1130."
FT /evidence="ECO:0000269|PubMed:17182608"
FT MUTAGEN 1127
FT /note="K->T: No effect on the interaction with RTN3; when
FT associated with T-1135."
FT /evidence="ECO:0000269|PubMed:17182608"
FT MUTAGEN 1130
FT /note="E->V: No effect on the interaction with RTN3; when
FT associated with E-1121."
FT /evidence="ECO:0000269|PubMed:17182608"
FT MUTAGEN 1135
FT /note="K->T: No effect on the interaction with RTN3; when
FT associated with T-1127."
FT /evidence="ECO:0000269|PubMed:17182608"
FT MUTAGEN 1136
FT /note="I->K: Loss of interaction with RTN3 and reduced
FT viral cytopathicity."
FT /evidence="ECO:0000269|PubMed:17182608"
FT MUTAGEN 1588
FT /note="H->D: Complete loss of DDX58 inhibition. Complete
FT loss of cleavage of host IRF7."
FT /evidence="ECO:0000269|PubMed:20519382"
FT MUTAGEN 1632
FT /note="R->Q: No effect on the ability to mediate DDX58
FT inhibition. No effect on the ability to cleave host IRF7."
FT /evidence="ECO:0000269|PubMed:20519382"
FT MUTAGEN 1695
FT /note="C->S: Complete loss of the ability to cleave host
FT PINX1."
FT /evidence="ECO:0000269|PubMed:27847364"
FT MUTAGEN 1702
FT /note="V->Q: No effect on the ability to cleave host PML."
FT /evidence="ECO:0000269|PubMed:34930370"
FT MUTAGEN 1702
FT /note="V->S: No effect on the ability to mediate DDX58
FT inhibition. No effect on the ability to cleave host IRF7."
FT /evidence="ECO:0000269|PubMed:20519382"
FT MUTAGEN 1989
FT /note="Y->S: Loss of host PPP1R15A translation activation."
FT /evidence="ECO:0000269|PubMed:34985336"
SQ SEQUENCE 2193 AA; 242852 MW; 0F0A58FB1A35A63F CRC64;
MGSQVSTQRS GSHENSNSAT EGSTINYTTI NYYKDSYAAT AGKQSLKQDP DKFANPVKDI
FTEMAAPLKS PSAEACGYSD RVAQLTIGNS TITTQEAANI IVGYGEWPSY CSDNDATAVD
KPTRPDVSVN RFYTLDTKLW EKSSKGWYWK FPDVLTETGV FGPNAQFHYL YRSGFCIHVQ
CNASKFHQGA LLVAVLPEYV IGTVAGGTGT ENSHPPYKQT QPGADGFELQ HPYVLDAGIP
ISQLTVCPHQ WINLRTNNCA TIIVPYMNTL PFDSALNHCN FGLLVVPISP LDFDQGATPV
IPITITLAPM CSEFAGLRQA VTQGFPTELK PGTNQFLTTD DGVSAPILPN FHPTPCIHIP
GEVRNLLELC QVETILEVNN VPTNATSLME RLRFPVSAQA GKGELCAVFR ADPGRDGPWQ
STMLGQLCGY YTQWSGSLEV TFMFTGSFMA TGKMLIAYTP PGGPLPKDRA TAMLGTHVIW
DFGLQSSVTL VIPWISNTHY RAHARDGVFD YYTTGLVSIW YQTNYVVPIG APNTAYIIAL
AAAQKNFTMK LCKDTSDILE TATIQGDRVA DVIESSIGDS VSKALTPALP APTGPDTQVS
SHRLDTGKVP ALQAAEIGAS SNASDESMIE TRCVLNSHST AETTLDSFFS RAGLVGEIDL
PLKGTTNPNG YANWDIDITG YAQMRRKVEL FTYMRFDAEF TFVACTPTGR VVPQLLQYMF
VPPGAPKPDS RDSLAWPTAT NPSVFVKSSD PPAQVSVPFM SPASAYQWFY DGYPTFGEHK
QEKDLEYGAC PNNMMGTFSV RTVGSSKSEY SLVIRIYMRM KHVRAWIPRP MRNQNYLFKS
NPNYAGDSIK PTGTSRTAIT TLGKFGQQSG AIYVGNFRVV NRHLATHTDW ANLVWEDSSR
DLLVSSTTAQ GCDTIARCNC QTGVYYCNSR RKHYPVSFSK PSLVFVEASE YYPARYQSHL
MLAEGHSEPG DCGGILRCQH GVVGIVSTGG SGLVGFADVR DLLWLDEEAM EQGVSDYIKG
LGRAFGTGFT DAVSREVEAL KNHLIGSEGA VEKILKNLVK LISALVIVIR SDYDMVTLTA
TLALIGCHGS PWAWIKSKTA SILGIPMAQK QSASWLKKFN DMANAAKGLE WIFNKISKFI
DWLKEKIIPA AKEKVEFLNN LKQLPLLENQ VSNLEQSAAS QEDLEAMFGN VIYLAHFCRK
FQPLYATEAK RVYALEKRMN NYMQFKSKHR IEPVCLIIRG SPGTGKSLAT GIIARAIADK
YRSSVYSLPP DPDHFDGYKQ QVVAVMDDLC QNPDGKDMSL FCQMVSTVDF VPPMASLEEK
GVSFTSKFVI ASTNASNIIV PTVSDSDAIR RRFYMDCDIE VTDSYKTDLG RLDAGRAAKL
CTENNTANFK RCSPLVCGKA IQLRDRKSKV RYSVDTVVSE LIREYNNRSA IGNTIEALFQ
GPPKFRPIRI SLEEKPAPDA ISDLLASVDS EEVRQYCREQ GWIIPETPTN VERHLNRAVL
VMQSIATVVA VVSLVYVIYK LFAGFQGAYS GAPKPILKKP VLRTATVQGP SLDFALSLLR
RNIRQAQTDQ GHFTMLGVRD RLAILPRHSQ PGKTIWVEHK LINVLDAVEL VDEQGVNLEL
TLVTLDTNEK FRDITKCIPE VITGASDATL VINTEHIPSM FVPVGDVVQY GFLNLSGKPT
HRTMMYNFPT KPGQCGGVVT SVGKIIGIHI GGNGRQAFCA GLKRSYFASE QGEIQWMKPN
RETGRLNING PTRTKLEPSV FHDVFEGNKE PAVLTSKDPR LEVDFEQALF SKYVGNTLHE
PDEYVTQAAL HYANQLKQLD INTSKMSMEE ACYGTEYLEA IDLHTSAGYP YSALGIKKRD
ILDPVTRDTS RMKLYMDKYG LDLPNSTYVK DELSSLDKIR KGESRLIEAS SLNDPVYPRL
TFGHLYEVFH ANPGTVTGSA VGCNPDVFWS KLPILLPGSL FAFDYSGYDA SLSPVWFRAL
ELVLREIGYS EEAVSLIEGI NHTHHVYRNK TYCVLGGMPS GCSGTSIFNS MINNIIIRTL
LIKTFKGIDL DELKMVAYGD DVLASYPFPI DCLEWGKTGK EYGLTMTPAD KSPCFNEVTW
ENATFLKRGF LPDHQFPFLI HPTMPMREIH ESIRWTKDAR NTQDHVRSLC LLAWHNGKEE
YEKFVSTIRS VPIGRALAIP NLENLRRNWL ELF
