POLG_CXB3N
ID POLG_CXB3N Reviewed; 2185 AA.
AC P03313; J9WSZ6; Q66322; Q66323; Q66324; Q66325; Q66326; Q66327; Q66328;
AC Q83744;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 205.
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 Coxsackievirus B3 (strain Nancy).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Picornavirales; Picornaviridae; Enterovirus; Enterovirus B.
OX NCBI_TaxID=103903;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2157045; DOI=10.1128/jvi.64.4.1573-1583.1990;
RA Klump W.M., Bergmann I., Mueller B.C., Ameis D., Kandolf R.;
RT "Complete nucleotide sequence of infectious Coxsackievirus B3 cDNA: two
RT initial 5' uridine residues are regained during plus-strand RNA
RT synthesis.";
RL J. Virol. 64:1573-1583(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=3027968; DOI=10.1016/0042-6822(87)90435-1;
RA Lindberg A.M., Staalhandske P.O.K., Pettersson U.;
RT "Genome of coxsackievirus B3.";
RL Virology 156:50-63(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1724-2185.
RX PubMed=6088796; DOI=10.1128/jvi.51.3.742-746.1984;
RA Staalhandske P.O.K., Lindberg A.M., Pettersson U.;
RT "Replicase gene of coxsackievirus B3.";
RL J. Virol. 51:742-746(1984).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Gangaplara A., Massilamany C., Vu H., Pattnaik A.K., Reddy J.;
RL Submitted (JUL-2012) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP INTERACTION WITH HOST CD55 (CAPSID PROTEIN VP1), AND FUNCTION (CAPSID
RP PROTEIN VP1).
RX PubMed=7538177; DOI=10.1128/jvi.69.6.3873-3877.1995;
RA Shafren D.R., Bates R.C., Agrez M.V., Herd R.L., Burns G.F., Barry R.D.;
RT "Coxsackieviruses B1, B3, and B5 use decay accelerating factor as a
RT receptor for cell attachment.";
RL J. Virol. 69:3873-3877(1995).
RN [6]
RP INTERACTION WITH HOST CXADR (CAPSID PROTEIN VP1), AND FUNCTION (CAPSID
RP PROTEIN VP1).
RX PubMed=10814575; DOI=10.1006/viro.2000.0324;
RA Martino T.A., Petric M., Weingartl H., Bergelson J.M., Opavsky M.A.,
RA Richardson C.D., Modlin J.F., Finberg R.W., Kain K.C., Willis N.,
RA Gauntt C.J., Liu P.P.;
RT "The coxsackie-adenovirus receptor (CAR) is used by reference strains and
RT clinical isolates representing all six serotypes of coxsackievirus group B
RT and by swine vesicular disease virus.";
RL Virology 271:99-108(2000).
RN [7]
RP INDUCTION.
RX PubMed=12384597; DOI=10.1093/nar/gkf583;
RA Ray P.S., Das S.;
RT "La autoantigen is required for the internal ribosome entry site-mediated
RT translation of Coxsackievirus B3 RNA.";
RL Nucleic Acids Res. 30:4500-4508(2002).
RN [8]
RP FUNCTION (PROTEIN 3A), AND INTERACTION WITH HOST GBF1 (PROTEIN 3A).
RX PubMed=17005635; DOI=10.1128/jvi.01225-06;
RA Wessels E., Duijsings D., Lanke K.H., van Dooren S.H., Jackson C.L.,
RA Melchers W.J., van Kuppeveld F.J.;
RT "Effects of picornavirus 3A Proteins on Protein Transport and GBF1-
RT dependent COP-I recruitment.";
RL J. Virol. 80:11852-11860(2006).
RN [9]
RP FUNCTION (PROTEASE 3C).
RX PubMed=18572216; DOI=10.1016/j.virol.2008.05.019;
RA de Breyne S., Bonderoff J.M., Chumakov K.M., Lloyd R.E., Hellen C.U.;
RT "Cleavage of eukaryotic initiation factor eIF5B by enterovirus 3C
RT proteases.";
RL Virology 378:118-122(2008).
RN [10]
RP FUNCTION (PROTEASE 3C), AND INTERACTION WITH HOST TICAM1 (PROTEASE 3C).
RX PubMed=21436888; DOI=10.1371/journal.ppat.1001311;
RA Mukherjee A., Morosky S.A., Delorme-Axford E., Dybdahl-Sissoko N.,
RA Oberste M.S., Wang T., Coyne C.B.;
RT "The coxsackievirus B 3C protease cleaves MAVS and TRIF to attenuate host
RT type I interferon and apoptotic signaling.";
RL PLoS Pathog. 7:E1001311-E1001311(2011).
RN [11]
RP INTERACTION WITH HOST ACBD3 (PROTEIN 3A).
RX PubMed=22258260; DOI=10.1128/jvi.06778-11;
RA Greninger A.L., Knudsen G.M., Betegon M., Burlingame A.L., Derisi J.L.;
RT "The 3A protein from multiple picornaviruses utilizes the golgi adaptor
RT protein ACBD3 to recruit PI4KIIIbeta.";
RL J. Virol. 86:3605-3616(2012).
RN [12]
RP COFACTOR.
RX PubMed=23667424; DOI=10.1371/journal.pone.0060272;
RA Gong P., Kortus M.G., Nix J.C., Davis R.E., Peersen O.B.;
RT "Structures of coxsackievirus, rhinovirus, and poliovirus polymerase
RT elongation complexes solved by engineering RNA mediated crystal contacts.";
RL PLoS ONE 8:E60272-E60272(2013).
RN [13]
RP FUNCTION (PROTEASE 2A), FUNCTION (PROTEASE 3C), AND MUTAGENESIS OF
RP CYS-1687.
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 [14]
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 [15]
RP INTERACTION WITH HOST ACBD3 (PROTEIN 3A), AND FUNCTION (PROTEIN 3A).
RX PubMed=31381608; DOI=10.1371/journal.ppat.1007962;
RA Horova V., Lyoo H., Rozycki B., Chalupska D., Smola M., Humpolickova J.,
RA Strating J.R.P.M., van Kuppeveld F.J.M., Boura E., Klima M.;
RT "Convergent evolution in the mechanisms of ACBD3 recruitment to
RT picornavirus replication sites.";
RL PLoS Pathog. 15:E1007962-E1007962(2019).
RN [16]
RP FUNCTION (PROTEASE 2A).
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 [17]
RP FUNCTION (PROTEASE 3C).
RX PubMed=33691586; DOI=10.1080/15548627.2021.1896925;
RA Mohamud Y., Tang H., Xue Y.C., Liu H., Ng C.S., Bahreyni A., Luo H.;
RT "Coxsackievirus B3 targets TFEB to disrupt lysosomal function.";
RL Autophagy 10:1-15(2021).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1541-1723.
RX PubMed=17037602; DOI=10.1007/978-0-387-33012-9_106;
RA Hilgenfeld R., Anand K., Mesters J.R., Rao Z., Shen X., Jiang H., Tan J.,
RA Verschueren K.H.;
RT "Structure and dynamics of SARS coronavirus main proteinase (Mpro).";
RL Adv. Exp. Med. Biol. 581:585-591(2006).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1724-2185 IN COMPLEX WITH VPG;
RP GTP AND DUTP, INTERACTION OF RNA-DIRECTED RNA POLYMERASE WITH VPG,
RP COFACTOR, AND FUNCTION (RNA-DIRECTED RNA POLYMERASE).
RX PubMed=18632861; DOI=10.1128/jvi.00631-08;
RA Gruez A., Selisko B., Roberts M., Bricogne G., Bussetta C., Jabafi I.,
RA Coutard B., De Palma A.M., Neyts J., Canard B.;
RT "The crystal structure of coxsackievirus B3 RNA-dependent RNA polymerase in
RT complex with its protein primer VPg confirms the existence of a second VPg
RT binding site on Picornaviridae polymerases.";
RL J. Virol. 82:9577-9590(2008).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.38 ANGSTROMS) OF 1541-1723.
RX PubMed=19144641; DOI=10.1074/jbc.m807947200;
RA Lee C.C., Kuo C.J., Ko T.P., Hsu M.F., Tsui Y.C., Chang S.C., Yang S.,
RA Chen S.J., Chen H.C., Hsu M.C., Shih S.R., Liang P.H., Wang A.H.;
RT "Structural basis of inhibition specificities of 3C and 3C-like proteases
RT by zinc-coordinating and peptidomimetic compounds.";
RL J. Biol. Chem. 284:7646-7655(2009).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1724-2185.
RX PubMed=25320316; DOI=10.1128/jvi.01574-14;
RA Campagnola G., McDonald S., Beaucourt S., Vignuzzi M., Peersen O.B.;
RT "Structure-function relationships underlying the replication fidelity of
RT viral RNA-dependent RNA polymerases.";
RL J. Virol. 89:275-286(2015).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 1724-2185.
RX PubMed=25799064; DOI=10.1371/journal.ppat.1004733;
RA van der Linden L., Vives-Adrian L., Selisko B., Ferrer-Orta C., Liu X.,
RA Lanke K., Ulferts R., De Palma A.M., Tanchis F., Goris N., Lefebvre D.,
RA De Clercq K., Leyssen P., Lacroix C., Purstinger G., Coutard B., Canard B.,
RA Boehr D.D., Arnold J.J., Cameron C.E., Verdaguer N., Neyts J.,
RA van Kuppeveld F.J.;
RT "The RNA template channel of the RNA-dependent RNA polymerase as a target
RT for development of antiviral therapy of multiple genera within a virus
RT family.";
RL PLoS Pathog. 11:E1004733-E1004733(2015).
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 interacts with host CD55 and CXADR
CC to provide virion attachment to target host cells (Probable). This
CC attachment induces virion internalization (By similarity). Tyrosine
CC kinases are probably involved in the entry process (By similarity).
CC After binding to its receptor, the capsid undergoes conformational
CC changes (By similarity). Capsid protein VP1 N-terminus (that contains
CC an 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:0000305|PubMed:10814575, ECO:0000305|PubMed:7538177}.
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). {ECO:0000250|UniProtKB:P03300}.
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). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000269|PubMed:24390337, 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. In turn, high levels of cytoplasmic calcium
CC may trigger membrane trafficking and transport of viral ER-associated
CC proteins to viroplasms, sites of viral genome replication.
CC {ECO:0000250|UniProtKB:P03300}.
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
CC (PubMed:17005635). This would result in depletion of MHC, trail
CC receptors and IFN receptors at the host cell surface (PubMed:17005635).
CC Plays an essential role in viral RNA replication by recruiting ACBD3
CC and PI4KB at the viral replication sites, thereby allowing the
CC formation of the rearranged membranous structures where viral
CC replication takes place (Probable). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000269|PubMed:17005635, ECO:0000305|PubMed:30755512,
CC ECO:0000305|PubMed:31381608}.
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. {ECO:0000250|UniProtKB:P03300}.
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 (PubMed:18572216). Cleaves
CC also host PABPC1, contributing to host translation shutoff (By
CC similarity). Cleaves and inhibits host DDX58/RIG-I, thereby inhibiting
CC the type-I IFN production and the establishment of the antiviral state
CC (PubMed:24390337). Cleaves and inhibits host MAVS, thereby inhibiting
CC the type-I IFN production and the establishment of the antiviral state
CC (PubMed:21436888). Cleaves and inhibits host TICAM1/TRIF, thereby
CC inhibiting the type-I IFN production (PubMed:21436888). Cleaves host
CC NLRP1, triggers host N-glycine-mediated degradation of the
CC autoinhibitory NLRP1 N-terminal fragment (By similarity). Cleaves host
CC transcription factor TFEB, thereby disrupting host lysosomal functions
CC and enhancing viral infection (PubMed:33691586).
CC {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03303,
CC ECO:0000269|PubMed:18572216, ECO:0000269|PubMed:21436888,
CC ECO:0000269|PubMed:24390337, ECO:0000269|PubMed:33691586}.
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. {ECO:0000250|UniProtKB:P03300}.
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:0000269|PubMed:18632861, ECO:0000269|PubMed:23667424};
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 (PubMed:18632861). {ECO:0000250|UniProtKB:P03300,
CC ECO:0000269|PubMed:18632861};
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 CD55 (Probable). Interacts with host CXADR (Probable).
CC {ECO:0000250|UniProtKB:P03300, ECO:0000305|PubMed:10814575,
CC ECO:0000305|PubMed:7538177}.
CC -!- SUBUNIT: [Capsid protein VP2]: Interacts with capsid protein VP1 and
CC capsid protein VP3 in the mature capsid.
CC {ECO:0000250|UniProtKB:P03300}.
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:P04936}.
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 (By similarity).
CC Interacts with capsid protein VP3; this interaction may be important
CC for virion morphogenesis (By similarity).
CC {ECO:0000250|UniProtKB:P03300}.
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 (PubMed:17005635). Interacts (via GOLD domain) with host ACBD3
CC (via GOLD domain); this interaction allows the formation of a viral
CC protein 3A/ACBD3 heterotetramer with a 2:2 stoichiometry, which will
CC stimulate the recruitment of host PI4KB in order to synthesize PI4P at
CC the viral RNA replication sites (PubMed:22258260, PubMed:31381608).
CC {ECO:0000250|UniProtKB:P03300, ECO:0000269|PubMed:17005635,
CC ECO:0000269|PubMed:22258260, ECO:0000269|PubMed:31381608}.
CC -!- SUBUNIT: [Viral protein genome-linked]: Interacts with RNA-directed RNA
CC polymerase. {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [Protease 3C]: Interacts with host TICAM1 (via C-terminus).
CC {ECO:0000269|PubMed:21436888}.
CC -!- SUBUNIT: [Protein 3CD]: Interacts with protein 3AB and with RNA-
CC directed RNA polymerase. {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase]: Interacts with Viral protein
CC genome-linked and with protein 3CD. {ECO:0000250|UniProtKB:P03300}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP0]: Virion. Host cytoplasm
CC {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP4]: Virion.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP2]: Virion
CC {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion
CC {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion
CC {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Protein 2B]: 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: [Protein 2C]: 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: [Protein 3A]: 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: [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:0000250|UniProtKB:Q66478}.
CC -!- SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm.
CC -!- SUBCELLULAR LOCATION: [Protein 3CD]: Host nucleus
CC {ECO:0000250|UniProtKB:P03300}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P03300}. 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}. 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 -!- 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:0000250|UniProtKB:P03300}.
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; M33854; AAA42931.1; -; Genomic_RNA.
DR EMBL; K02709; AAA42932.1; -; Genomic_RNA.
DR EMBL; M16572; AAA74400.1; -; Genomic_RNA.
DR EMBL; JX312064; AFS18536.1; -; Genomic_RNA.
DR PIR; A26354; GNNYB3.
DR PIR; A34664; GNNYBT.
DR PDB; 2VB0; X-ray; 2.40 A; A=1541-1723.
DR PDB; 2ZTX; X-ray; 1.72 A; A=1541-1723.
DR PDB; 2ZTY; X-ray; 1.72 A; A=1541-1723.
DR PDB; 2ZTZ; X-ray; 2.00 A; A/B=1541-1723.
DR PDB; 2ZU1; X-ray; 1.38 A; A/B=1541-1723.
DR PDB; 2ZU3; X-ray; 1.75 A; A=1541-1723.
DR PDB; 3CDU; X-ray; 2.10 A; A=1724-2185.
DR PDB; 3CDW; X-ray; 2.50 A; A=1724-2185, H=1519-1540.
DR PDB; 4WFX; X-ray; 1.81 A; A=1724-2185.
DR PDB; 4WFY; X-ray; 2.06 A; A=1724-2185.
DR PDB; 4WFZ; X-ray; 1.80 A; A=1724-2185.
DR PDB; 4Y2A; X-ray; 2.90 A; A=1724-2185.
DR PDB; 6S3A; X-ray; 1.52 A; A=1216-1429.
DR PDB; 6T3W; X-ray; 1.82 A; A=1216-1429.
DR PDB; 7QUW; X-ray; 1.65 A; AAA=1541-1720.
DR PDBsum; 2VB0; -.
DR PDBsum; 2ZTX; -.
DR PDBsum; 2ZTY; -.
DR PDBsum; 2ZTZ; -.
DR PDBsum; 2ZU1; -.
DR PDBsum; 2ZU3; -.
DR PDBsum; 3CDU; -.
DR PDBsum; 3CDW; -.
DR PDBsum; 4WFX; -.
DR PDBsum; 4WFY; -.
DR PDBsum; 4WFZ; -.
DR PDBsum; 4Y2A; -.
DR PDBsum; 6S3A; -.
DR PDBsum; 6T3W; -.
DR PDBsum; 7QUW; -.
DR SMR; P03313; -.
DR BindingDB; P03313; -.
DR ChEMBL; CHEMBL2396505; -.
DR MEROPS; C03.011; -.
DR MEROPS; C03.020; -.
DR SABIO-RK; P03313; -.
DR EvolutionaryTrace; P03313; -.
DR Proteomes; UP000007760; Genome.
DR Proteomes; UP000181225; Genome.
DR Proteomes; UP000181606; Genome.
DR GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IDA:CACAO.
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:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0075509; P:endocytosis involved in viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0039520; P:induction by virus of host autophagy; ISS:UniProtKB.
DR GO; GO:0039656; P:modulation by virus of host gene expression; IDA:BHF-UCL.
DR GO; GO:0061765; P:modulation by virus of host NIK/NF-kappaB cascade; IDA:BHF-UCL.
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; 4.10.80.10; -; 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; IPR036988; Pico_P1A_sf.
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 3D-structure; Activation of host autophagy by virus; ATP-binding;
KW Autocatalytic cleavage; Capsid protein; Covalent protein-RNA linkage;
KW DNA replication; 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; Myristate; Nucleotide-binding; Nucleotidyltransferase;
KW Phosphoprotein; Pore-mediated penetration of viral genome into host cell;
KW Protease; Repeat; 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..2185
FT /note="Genome polyprotein"
FT /id="PRO_0000426266"
FT CHAIN 2..851
FT /note="P1"
FT /id="PRO_0000426267"
FT CHAIN 2..332
FT /note="Capsid protein VP0"
FT /id="PRO_0000426268"
FT CHAIN 2..69
FT /note="Capsid protein VP4"
FT /id="PRO_0000426269"
FT CHAIN 70..332
FT /note="Capsid protein VP2"
FT /id="PRO_0000426270"
FT CHAIN 333..570
FT /note="Capsid protein VP3"
FT /id="PRO_0000426271"
FT CHAIN 571..851
FT /note="Capsid protein VP1"
FT /id="PRO_0000426272"
FT CHAIN 852..1429
FT /note="P2"
FT /id="PRO_0000426273"
FT CHAIN 852..1001
FT /note="Protease 2A"
FT /id="PRO_0000426274"
FT CHAIN 1002..1100
FT /note="Protein 2B"
FT /id="PRO_0000039587"
FT CHAIN 1101..1429
FT /note="Protein 2C"
FT /id="PRO_0000039588"
FT CHAIN 1430..2185
FT /note="P3"
FT /id="PRO_0000426275"
FT CHAIN 1430..1540
FT /note="Protein 3AB"
FT /id="PRO_0000426276"
FT CHAIN 1430..1518
FT /note="Protein 3A"
FT /id="PRO_0000039589"
FT CHAIN 1519..1540
FT /note="Viral protein genome-linked"
FT /id="PRO_0000426277"
FT CHAIN 1541..2185
FT /note="Protein 3CD"
FT /id="PRO_0000426278"
FT CHAIN 1541..1723
FT /note="Protease 3C"
FT /id="PRO_0000426279"
FT CHAIN 1724..2185
FT /note="RNA-directed RNA polymerase"
FT /id="PRO_0000426280"
FT TOPO_DOM 2..1495
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 1496..1511
FT /evidence="ECO:0000255"
FT TOPO_DOM 1512..2185
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1205..1361
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DOMAIN 1541..1719
FT /note="Peptidase C3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT DOMAIN 1950..2066
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT ZN_FING 1369..1386
FT /note="C4-type; degenerate"
FT /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT REGION 568..584
FT /note="Amphipathic alpha-helix"
FT /evidence="ECO:0000255"
FT REGION 1101..1239
FT /note="Oligomerization"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT REGION 1101..1173
FT /note="Membrane-binding"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT REGION 1122..1126
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT REGION 1413..1420
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT REGION 1424..1429
FT /note="Oligomerization"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT ACT_SITE 872
FT /note="For protease 2A activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT ACT_SITE 890
FT /note="For protease 2A activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT ACT_SITE 961
FT /note="For protease 2A activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT ACT_SITE 1580
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT ACT_SITE 1611
FT /note="For protease 3C activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT ACT_SITE 1687
FT /note="For protease 3C activity"
FT /evidence="ECO:0000269|PubMed:33691586"
FT BINDING 907
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 909
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 967
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 969
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 1369
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B9VUU3"
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 1386
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT BINDING 1956
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000305|PubMed:23667424"
FT BINDING 1956
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000305|PubMed:23667424"
FT BINDING 2052
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 2052
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 69..70
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT SITE 332..333
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 851..852
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1001..1002
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1100..1101
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1125
FT /note="Involved in the interaction with host RTN3"
FT /evidence="ECO:0000250|UniProtKB:Q66478"
FT SITE 1429..1430
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1518..1519
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1540..1541
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT SITE 1723..1724
FT /note="Cleavage; by protease 3C"
FT /evidence="ECO:0000250|UniProtKB:P03301"
FT MOD_RES 1521
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 1687
FT /note="C->A: Loss of host TFEB cleavage activity."
FT /evidence="ECO:0000269|PubMed:24390337"
FT CONFLICT 16
FT /note="R -> G (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 177
FT /note="V -> D (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="T -> S (in Ref. 4; AFS18536)"
FT /evidence="ECO:0000305"
FT CONFLICT 469
FT /note="P -> L (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 487
FT /note="I -> V (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 510
FT /note="F -> Y (in Ref. 2; AAA74400 and 4; AFS18536)"
FT /evidence="ECO:0000305"
FT CONFLICT 516
FT /note="Y -> C (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 566
FT /note="Q -> E (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 593
FT /note="T -> N (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 650
FT /note="K -> E (in Ref. 2; AAA74400 and 4; AFS18536)"
FT /evidence="ECO:0000305"
FT CONFLICT 854..865
FT /note="FGQQSGAVYVGN -> IWTTIRGSVCGD (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 873
FT /note="L -> S (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 1097
FT /note="A -> P (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 1280
FT /note="Q -> H (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 1437
FT /note="I -> F (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 1449
FT /note="P -> L (in Ref. 4; AFS18536)"
FT /evidence="ECO:0000305"
FT CONFLICT 1503
FT /note="V -> M (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 1616
FT /note="K -> E (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 1624
FT /note="R -> G (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 1627
FT /note="R -> G (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 1630
FT /note="L -> V (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 1718
FT /note="Y -> N (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 1734
FT /note="D -> V (in Ref. 2; AAA74400)"
FT /evidence="ECO:0000305"
FT CONFLICT 1758
FT /note="E -> V (in Ref. 2 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 1824
FT /note="V -> R (in Ref. 2 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 1867
FT /note="C -> R (in Ref. 2 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 1880
FT /note="Y -> H (in Ref. 2 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 2001
FT /note="D -> N (in Ref. 2 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 2095
FT /note="A -> V (in Ref. 2 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 2115
FT /note="V -> A (in Ref. 2 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 2175
FT /note="S -> T (in Ref. 2 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 2178
FT /note="R -> G (in Ref. 2 and 3)"
FT /evidence="ECO:0000305"
FT STRAND 1223..1228
FT /evidence="ECO:0007829|PDB:6S3A"
FT HELIX 1235..1249
FT /evidence="ECO:0007829|PDB:6S3A"
FT STRAND 1254..1256
FT /evidence="ECO:0007829|PDB:6S3A"
FT STRAND 1259..1262
FT /evidence="ECO:0007829|PDB:6T3W"
FT TURN 1263..1266
FT /evidence="ECO:0007829|PDB:6T3W"
FT STRAND 1271..1278
FT /evidence="ECO:0007829|PDB:6S3A"
FT HELIX 1284..1293
FT /evidence="ECO:0007829|PDB:6S3A"
FT STRAND 1294..1297
FT /evidence="ECO:0007829|PDB:6S3A"
FT HELIX 1304..1306
FT /evidence="ECO:0007829|PDB:6S3A"
FT STRAND 1316..1323
FT /evidence="ECO:0007829|PDB:6S3A"
FT HELIX 1332..1341
FT /evidence="ECO:0007829|PDB:6S3A"
FT STRAND 1343..1350
FT /evidence="ECO:0007829|PDB:6S3A"
FT HELIX 1352..1354
FT /evidence="ECO:0007829|PDB:6S3A"
FT HELIX 1362..1366
FT /evidence="ECO:0007829|PDB:6S3A"
FT STRAND 1376..1380
FT /evidence="ECO:0007829|PDB:6S3A"
FT TURN 1383..1385
FT /evidence="ECO:0007829|PDB:6S3A"
FT STRAND 1386..1394
FT /evidence="ECO:0007829|PDB:6S3A"
FT TURN 1395..1397
FT /evidence="ECO:0007829|PDB:6S3A"
FT HELIX 1403..1418
FT /evidence="ECO:0007829|PDB:6S3A"
FT HELIX 1420..1425
FT /evidence="ECO:0007829|PDB:6S3A"
FT HELIX 1426..1428
FT /evidence="ECO:0007829|PDB:6S3A"
FT TURN 1528..1530
FT /evidence="ECO:0007829|PDB:3CDW"
FT HELIX 1542..1554
FT /evidence="ECO:0007829|PDB:2ZU1"
FT STRAND 1555..1560
FT /evidence="ECO:0007829|PDB:2ZU1"
FT STRAND 1563..1572
FT /evidence="ECO:0007829|PDB:2ZU1"
FT STRAND 1574..1578
FT /evidence="ECO:0007829|PDB:2ZU1"
FT HELIX 1579..1581
FT /evidence="ECO:0007829|PDB:2ZU1"
FT STRAND 1585..1589
FT /evidence="ECO:0007829|PDB:2ZU1"
FT STRAND 1592..1603
FT /evidence="ECO:0007829|PDB:2ZU1"
FT STRAND 1609..1617
FT /evidence="ECO:0007829|PDB:2ZU1"
FT HELIX 1627..1629
FT /evidence="ECO:0007829|PDB:2ZU1"
FT STRAND 1637..1644
FT /evidence="ECO:0007829|PDB:2ZU1"
FT STRAND 1646..1649
FT /evidence="ECO:0007829|PDB:2ZU1"
FT STRAND 1652..1667
FT /evidence="ECO:0007829|PDB:2ZU1"
FT STRAND 1670..1680
FT /evidence="ECO:0007829|PDB:2ZU1"
FT STRAND 1690..1693
FT /evidence="ECO:0007829|PDB:2ZU1"
FT STRAND 1696..1705
FT /evidence="ECO:0007829|PDB:2ZU1"
FT STRAND 1708..1713
FT /evidence="ECO:0007829|PDB:2ZU1"
FT HELIX 1716..1719
FT /evidence="ECO:0007829|PDB:2ZU1"
FT STRAND 1725..1731
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 1732..1735
FT /evidence="ECO:0007829|PDB:4WFZ"
FT TURN 1752..1756
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 1761..1763
FT /evidence="ECO:0007829|PDB:4Y2A"
FT HELIX 1777..1782
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 1795..1809
FT /evidence="ECO:0007829|PDB:4WFZ"
FT TURN 1810..1812
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 1820..1825
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 1835..1837
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 1843..1845
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 1850..1853
FT /evidence="ECO:0007829|PDB:4WFZ"
FT TURN 1856..1859
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 1862..1871
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 1877..1881
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 1885..1887
FT /evidence="ECO:0007829|PDB:4Y2A"
FT HELIX 1888..1892
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 1898..1901
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 1904..1923
FT /evidence="ECO:0007829|PDB:4WFZ"
FT TURN 1927..1930
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 1937..1947
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 1950..1953
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 1955..1959
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 1960..1963
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 1966..1978
FT /evidence="ECO:0007829|PDB:4WFZ"
FT TURN 1983..1986
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 1987..1993
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 1994..1999
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 2002..2008
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 2017..2036
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 2042..2044
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 2046..2050
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 2053..2060
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 2064..2073
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 2078..2080
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 2083..2085
FT /evidence="ECO:0007829|PDB:4WFZ"
FT TURN 2092..2094
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 2100..2104
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 2106..2108
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 2111..2115
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 2118..2125
FT /evidence="ECO:0007829|PDB:4WFZ"
FT STRAND 2127..2129
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 2131..2133
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 2134..2145
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 2146..2148
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 2150..2160
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 2164..2168
FT /evidence="ECO:0007829|PDB:4WFZ"
FT HELIX 2174..2184
FT /evidence="ECO:0007829|PDB:4WFZ"
SQ SEQUENCE 2185 AA; 243453 MW; 1B5ECE3DA47338FF CRC64;
MGAQVSTQKT GAHETRLNAS GNSIIHYTNI NYYKDAASNS ANRQDFTQDP GKFTEPVKDI
MIKSLPALNS PTVEECGYSD RARSITLGNS TITTQECANV VVGYGVWPDY LKDSEATAED
QPTQPDVATC RFYTLDSVQW QKTSPGWWWK LPDALSNLGL FGQNMQYHYL GRTGYTVHVQ
CNASKFHQGC LLVVCVPEAE MGCATLDNTP SSAELLGGDT AKEFADKPVA SGSNKLVQRV
VYNAGMGVGV GNLTIFPHQW INLRTNNSAT IVMPYTNSVP MDNMFRHNNV TLMVIPFVPL
DYCPGSTTYV PITVTIAPMC AEYNGLRLAG HQGLPTMNTP GSCQFLTSDD FQSPSAMPQY
DVTPEMRIPG EVKNLMEIAE VDSVVPVQNV GEKVNSMEAY QIPVRSNEGS GTQVFGFPLQ
PGYSSVFSRT LLGEILNYYT HWSGSIKLTF MFCGSAMATG KFLLAYSPPG AGAPTKRVDA
MLGTHVIWDV GLQSSCVLCI PWISQTHYRF VASDEYTAGG FITCWYQTNI VVPADAQSSC
YIMCFVSACN DFSVRLLKDT PFISQQNFFQ GPVEDAITAA IGRVADTVGT GPTNSEAIPA
LTAAETGHTS QVVPGDTMQT RHVKNYHSRS ESTIENFLCR SACVYFTEYK NSGAKRYAEW
VLTPRQAAQL RRKLEFFTYV RFDLELTFVI TSTQQPSTTQ NQDAQILTHQ IMYVPPGGPV
PDKVDSYVWQ TSTNPSVFWT EGNAPPRMSI PFLSIGNAYS NFYDGWSEFS RNGVYGINTL
NNMGTLYARH VNAGSTGPIK STIRIYFKPK HVKAWIPRPP RLCQYEKAKN VNFQPSGVTT
TRQSITTMTN TGAFGQQSGA VYVGNYRVVN RHLATSADWQ NCVWESYNRD LLVSTTTAHG
CDIIARCQCT TGVYFCASKN KHYPISFEGP GLVEVQESEY YPRRYQSHVL LAAGFSEPGD
CGGILRCEHG VIGIVTMGGE GVVGFADIRD LLWLEDDAME QGVKDYVEQL GNAFGSGFTN
QICEQVNLLK ESLVGQDSIL EKSLKALVKI ISALVIVVRN HDDLITVTAT LALIGCTSSP
WRWLKQKVSQ YYGIPMAERQ NNSWLKKFTE MTNACKGMEW IAVKIQKFIE WLKVKILPEV
REKHEFLNRL KQLPLLESQI ATIEQSAPSQ SDQEQLFSNV QYFAHYCRKY APLYAAEAKR
VFSLEKKMSN YIQFKSKCRI EPVCLLLHGS PGAGKSVATN LIGRSLAEKL NSSVYSLPPD
PDHFDGYKQQ AVVIMDDLCQ NPDGKDVSLF CQMVSSVDFV PPMAALEEKG ILFTSPFVLA
STNAGSINAP TVSDSRALAR RFHFDMNIEV ISMYSQNGKI NMPMSVKTCD DECCPVNFKK
CCPLVCGKAI QFIDRRTQVR YSLDMLVTEM FREYNHRHSV GTTLEALFQG PPVYREIKIS
VAPETPPPPA IADLLKSVDS EAVREYCKEK GWLVPEINST LQIEKHVSRA FICLQALTTF
VSVAGIIYII YKLFAGFQGA YTGVPNQKPR VPTLRQAKVQ GPAFEFAVAM MKRNSSTVKT
EYGEFTMLGI YDRWAVLPRH AKPGPTILMN DQEVGVLDAK ELVDKDGTNL ELTLLKLNRN
EKFRDIRGFL AKEEVEVNEA VLAINTSKFP NMYIPVGQVT EYGFLNLGGT PTKRMLMYNF
PTRAGQCGGV LMSTGKVLGI HVGGNGHQGF SAALLKHYFN DEQGEIEFIE SSKDAGFPVI
NTPSKTKLEP SVFHQVFEGN KEPAVLRSGD PRLKANFEEA IFSKYIGNVN THVDEYMLEA
VDHYAGQLAT LDISTEPMKL EDAVYGTEGL EALDLTTSAG YPYVALGIKK RDILSKKTKD
LTKLKECMDK YGLNLPMVTY VKDELRSIEK VAKGKSRLIE ASSLNDSVAM RQTFGNLYKT
FHLNPGVVTG SAVGCDPDLF WSKIPVMLDG HLIAFDYSGY DASLSPVWFA CLKMLLEKLG
YTHKETNYID YLCNSHHLYR DKHYFVRGGM PSGCSGTSIF NSMINNIIIR TLMLKVYKGI
DLDQFRMIAY GDDVIASYPW PIDASLLAEA GKGYGLIMTP ADKGECFNEV TWTNATFLKR
YFRADEQYPF LVHPVMPMKD IHESIRWTKD PKNTQDHVRS LCLLAWHNGE HEYEEFIRKI
RSVPVGRCLT LPAFSTLRRK WLDSF
