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   24-JAN-2024, entry version 213.
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; Ensavirinae; 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=33410748; DOI=10.7554/elife.60609;
RA   Tsu B.V., Beierschmitt C., Ryan A.P., Agarwal R., Mitchell P.S.,
RA   Daugherty M.D.;
RT   "Diverse viral proteases activate the NLRP1 inflammasome.";
RL   Elife 10:0-0(2021).
RN   [18]
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   [19]
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   [20]
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   [21]
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   [22]
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   [23]
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 RIGI, thereby inhibiting the
CC       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 (PubMed:33410748). Cleaves
CC       host transcription factor TFEB, thereby disrupting host lysosomal
CC       functions 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:33410748,
CC       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; 7LMS; EM; 3.50 A; B=855-1001.
DR   PDB; 7QUW; X-ray; 1.65 A; AAA=1541-1720.
DR   PDB; 7W0Q; X-ray; 1.10 A; B=1420-1429.
DR   PDB; 7W0S; X-ray; 1.40 A; A/D/F=1420-1429.
DR   PDB; 7W0T; X-ray; 1.57 A; A/D/E=1420-1429.
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; 7LMS; -.
DR   PDBsum; 7QUW; -.
DR   PDBsum; 7W0Q; -.
DR   PDBsum; 7W0S; -.
DR   PDBsum; 7W0T; -.
DR   EMDB; EMD-23441; -.
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: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:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0005216; F:monoatomic ion channel activity; IEA:UniProtKB-KW.
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-dependent 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:0006351; P:DNA-templated transcription; IEA:InterPro.
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:perturbation by virus of host non-canonical NF-kappaB signal transduction; IDA:BHF-UCL.
DR   GO; GO:0044694; P:pore-mediated entry of viral genome into host cell; IEA:UniProtKB-KW.
DR   GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW.
DR   GO; GO:0039522; P:suppression by virus of host mRNA export from nucleus; IEA:UniProtKB-KW.
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:0039694; P:viral RNA genome replication; IEA:InterPro.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR   GO; GO:0039707; P:virus-mediated pore formation in host cell membrane; IEA:UniProtKB-KW.
DR   CDD; cd23213; Enterovirus_RdRp; 1.
DR   CDD; cd00205; rhv_like; 3.
DR   Gene3D; 1.20.960.20; -; 1.
DR   Gene3D; 2.60.120.20; -; 3.
DR   Gene3D; 3.30.70.270; -; 1.
DR   Gene3D; 4.10.80.10; Picornavirus coat protein VP4; 1.
DR   Gene3D; 6.10.20.20; Poliovirus 3A protein-like; 1.
DR   Gene3D; 4.10.880.10; Poliovirus 3D polymerase Domain 1 (Nucleotidyltransferase); 2.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 4.
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; SSF56672; DNA/RNA polymerases; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   SUPFAM; SSF88633; Positive stranded ssRNA viruses; 2.
DR   SUPFAM; SSF89043; Soluble domain of poliovirus core protein 3a; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 2.
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          860..863
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   STRAND          866..870
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   HELIX           871..873
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   HELIX           876..880
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   STRAND          882..886
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   HELIX           887..889
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   STRAND          891..895
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   STRAND          910..915
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   TURN            917..919
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   STRAND          921..926
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   STRAND          928..935
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   STRAND          943..953
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   HELIX           958..960
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   STRAND          964..967
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   STRAND          970..977
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   STRAND          982..987
FT                   /evidence="ECO:0007829|PDB:7LMS"
FT   HELIX           992..994
FT                   /evidence="ECO:0007829|PDB:7LMS"
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           1425..1428
FT                   /evidence="ECO:0007829|PDB:7W0Q"
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
//