ID   POLG_HED68              Reviewed;        2188 AA.
AC   Q68T42;
DT   26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2004, sequence version 1.
DT   29-SEP-2021, entry version 143.
DE   RecName: Full=Genome polyprotein;
DE   Contains:
DE     RecName: Full=P1;
DE   Contains:
DE     RecName: Full=Capsid protein VP0;
DE     AltName: Full=VP4-VP2;
DE   Contains:
DE     RecName: Full=Capsid protein VP4;
DE     AltName: Full=P1A;
DE     AltName: Full=Virion protein 4;
DE   Contains:
DE     RecName: Full=Capsid protein VP2;
DE     AltName: Full=P1B;
DE     AltName: Full=Virion protein 2;
DE   Contains:
DE     RecName: Full=Capsid protein VP3;
DE     AltName: Full=P1C;
DE     AltName: Full=Virion protein 3;
DE   Contains:
DE     RecName: Full=Capsid protein VP1;
DE     AltName: Full=P1D;
DE     AltName: Full=Virion protein 1;
DE   Contains:
DE     RecName: Full=P2;
DE   Contains:
DE     RecName: Full=Protease 2A;
DE              Short=P2A;
DE              EC=3.4.22.29 {ECO:0000250|UniProtKB:P03300};
DE     AltName: Full=Picornain 2A;
DE     AltName: Full=Protein 2A;
DE   Contains:
DE     RecName: Full=Protein 2B;
DE              Short=P2B;
DE   Contains:
DE     RecName: Full=Protein 2C;
DE              Short=P2C;
DE              EC=3.6.1.15 {ECO:0000250|UniProtKB:P03300};
DE   Contains:
DE     RecName: Full=P3;
DE   Contains:
DE     RecName: Full=Protein 3AB;
DE   Contains:
DE     RecName: Full=Protein 3A;
DE              Short=P3A;
DE   Contains:
DE     RecName: Full=Viral protein genome-linked;
DE              Short=VPg;
DE     AltName: Full=Protein 3B;
DE              Short=P3B;
DE   Contains:
DE     RecName: Full=Protein 3CD;
DE              EC=3.4.22.28;
DE   Contains:
DE     RecName: Full=Protease 3C {ECO:0000255|PROSITE-ProRule:PRU01222};
DE              EC=3.4.22.28 {ECO:0000255|PROSITE-ProRule:PRU01222};
DE     AltName: Full=Picornain 3C {ECO:0000255|PROSITE-ProRule:PRU01222};
DE              Short=P3C {ECO:0000255|PROSITE-ProRule:PRU01222};
DE   Contains:
DE     RecName: Full=RNA-directed RNA polymerase {ECO:0000255|PROSITE-ProRule:PRU00539};
DE              Short=RdRp;
DE              EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
DE     AltName: Full=3D polymerase;
DE              Short=3Dpol;
DE     AltName: Full=Protein 3D;
DE              Short=3D;
OS   Human enterovirus D68 (EV68) (EV-68).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Picornavirales; Picornaviridae; Enterovirus; Enterovirus D.
OX   NCBI_TaxID=42789;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Fermon;
RX   PubMed=15302951; DOI=10.1099/vir.0.79925-0;
RA   Oberste M.S., Maher K., Schnurr D., Flemister M.R., Lovchik J.C.,
RA   Peters H., Sessions W., Kirk C., Chatterjee N., Fuller S., Hanauer J.M.,
RA   Pallansch M.A.;
RT   "Enterovirus 68 is associated with respiratory illness and shares
RT   biological features with both the enteroviruses and the rhinoviruses.";
RL   J. Gen. Virol. 85:2577-2584(2004).
RN   [2]
RP   FUNCTION (PROTEASE 3C).
RC   STRAIN=Beijing;
RX   PubMed=24672048; DOI=10.1128/jvi.03138-13;
RA   Xiang Z., Li L., Lei X., Zhou H., Zhou Z., He B., Wang J.;
RT   "Enterovirus 68 3C protease cleaves TRIF to attenuate antiviral responses
RT   mediated by Toll-like receptor 3.";
RL   J. Virol. 88:6650-6659(2014).
RN   [3]
RP   FUNCTION (PROTEASE 3C).
RX   PubMed=26608321; DOI=10.1128/jvi.02395-15;
RA   Xiang Z., Liu L., Lei X., Zhou Z., He B., Wang J.;
RT   "3C Protease of Enterovirus D68 Inhibits Cellular Defense Mediated by
RT   Interferon Regulatory Factor 7.";
RL   J. Virol. 90:1613-1621(2016).
RN   [4]
RP   INTERACTION WITH HOST IFIH1 (PROTEASE 3C), AND FUNCTION (PROTEASE 3C).
RC   STRAIN=Fermon;
RX   PubMed=28424289; DOI=10.1128/jvi.00546-17;
RA   Rui Y., Su J., Wang H., Chang J., Wang S., Zheng W., Cai Y., Wei W.,
RA   Gordy J.T., Markham R., Kong W., Zhang W., Yu X.F.;
RT   "Disruption of MDA5-Mediated Innate Immune Responses by the 3C Proteins of
RT   Coxsackievirus A16, Coxsackievirus A6, and Enterovirus D68.";
RL   J. Virol. 91:0-0(2017).
RN   [5]
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   [6] {ECO:0007744|PDB:5BNN, ECO:0007744|PDB:5BNO, ECO:0007744|PDB:5BNP}
RP   X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 565-861; 70-317; 318-564 AND
RP   2-69, FUNCTION (CAPSID PROTEIN VP1), AND FUNCTION (CAPSID PROTEIN VP3).
RX   PubMed=26563423; DOI=10.1038/ncomms9865;
RA   Liu Y., Sheng J., Baggen J., Meng G., Xiao C., Thibaut H.J.,
RA   van Kuppeveld F.J., Rossmann M.G.;
RT   "Sialic acid-dependent cell entry of human enterovirus D68.";
RL   Nat. Commun. 6:8865-8865(2015).
RN   [7] {ECO:0007744|PDB:4WM7, ECO:0007744|PDB:4WM8}
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 70-317 AND 318-564 IN COMPLEX
RP   WITH PLECONARIL.
RX   PubMed=25554786; DOI=10.1126/science.1261962;
RA   Liu Y., Sheng J., Fokine A., Meng G., Shin W.H., Long F., Kuhn R.J.,
RA   Kihara D., Rossmann M.G.;
RT   "Structure and inhibition of EV-D68, a virus that causes respiratory
RT   illness in children.";
RL   Science 347:71-74(2015).
RN   [8] {ECO:0007744|PDB:6HLN}
RP   X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1438-1497, INTERACTION WITH HOST
RP   ACBD3 (PROTEIN 3A), SUBUNIT, MUTAGENESIS OF 1460-ASN--ASP-1462;
RP   1469-GLN--ASP-1473; 1481-ILE--HIS-1484 AND 1489-LEU--LYS-1493, AND FUNCTION
RP   (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).
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: [Capsid protein VP1]: Forms an icosahedral capsid of pseudo
CC       T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The
CC       capsid is 300 Angstroms in diameter, composed of 60 copies of each
CC       capsid protein and enclosing the viral positive strand RNA genome (By
CC       similarity). Capsid protein VP1 mainly forms the vertices of the capsid
CC       (By similarity). Capsid protein VP1, together with VP3, interacts with
CC       host cell sialic acids to provide virion attachment to target host
CC       cells (PubMed:26563423). This attachment induces virion internalization
CC       (PubMed:26563423). After binding to its receptor, the capsid undergoes
CC       conformational changes (By similarity). Capsid protein VP1 N-terminus
CC       (that contains an amphipathic alpha-helix) and capsid protein VP4 are
CC       externalized (By similarity). Together, they shape a pore in the host
CC       membrane through which viral genome is translocated to host cell
CC       cytoplasm (By similarity). {ECO:0000250|UniProtKB:P03300,
CC       ECO:0000269|PubMed:26563423}.
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). Capsid protein VP3, together with VP1, interacts with host
CC       cell sialic acids to provide virion attachment to target host cells
CC       (PubMed:26563423). {ECO:0000250|UniProtKB:P03300,
CC       ECO:0000269|PubMed:26563423}.
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: [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). {ECO:0000250|UniProtKB:P03300,
CC       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 (By
CC       similarity). This would result in depletion of MHC, trail receptors and
CC       IFN receptors at the host cell surface (By similarity). Plays an
CC       essential role in viral RNA replication by recruiting ACBD3 and PI4KB
CC       at the viral replication sites, thereby allowing the formation of the
CC       rearranged membranous structures where viral replication takes place
CC       (PubMed:31381608). {ECO:0000250|UniProtKB:P03300,
CC       ECO:0000269|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 (By similarity). Cleaves also
CC       host PABPC1, contributing to host translation shutoff (By similarity).
CC       Binds and inhibits host IFIH1/MDA5, thereby inhibiting the type-I IFN
CC       production and the establishment of the antiviral state
CC       (PubMed:28424289). Cleaves host MAP3K7/TAK1, resulting in inhibition of
CC       TRAF6-triggered NF-kappa-B induction (PubMed:28424289). Cleaves host
CC       TICAM1; this interaction allows the virus to disrupt host TLR3
CC       signaling (PubMed:24672048). Cleaves host IRF7, resulting in inhibition
CC       of type-I IFN production (PubMed:26608321). Cleaves host NLRP1,
CC       triggers host N-glycine-mediated degradation of the autoinhibitory
CC       NLRP1 N-terminal fragment (By similarity).
CC       {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03303,
CC       ECO:0000269|PubMed:24672048, ECO:0000269|PubMed:26608321,
CC       ECO:0000269|PubMed:28424289}.
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:0000250|UniProtKB:P03300};
CC       Note=Binds 2 magnesium ions that constitute a dinuclear catalytic metal
CC       center (By similarity). The magnesium ions are not prebound but only
CC       present for catalysis (By similarity). Requires the presence of 3CDpro
CC       or 3CPro (By similarity). {ECO:0000250|UniProtKB:P03300,
CC       ECO:0000250|UniProtKB:P03313};
CC   -!- 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).
CC       {ECO:0000250|UniProtKB:P03300}.
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 (PubMed:31381608). Interacts with host
CC       GBF1 (By similarity). Interacts (via GOLD domain) with host ACBD3 (via
CC       GOLD domain); this interaction allows the formation of a viral protein
CC       3A/ACBD3 heterotetramer with a 2:2 stoichiometry, which will stimulate
CC       the recruitment of host PI4KB in order to synthesize PI4P at the viral
CC       RNA replication sites (PubMed:31381608). {ECO:0000250|UniProtKB:P03300,
CC       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 IFIH1/MDA5; this
CC       interaction inhibits host IFIH1. {ECO:0000269|PubMed:28424289}.
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; AY426531; AAR98503.1; -; Genomic_RNA.
DR   PDB; 4WM7; X-ray; 2.32 A; B=70-317, C=318-564.
DR   PDB; 4WM8; X-ray; 2.00 A; B=70-317, C=318-564.
DR   PDB; 5BNN; X-ray; 2.32 A; A=565-861, B=70-317, C=318-564, D=2-69.
DR   PDB; 5BNO; X-ray; 2.15 A; A=565-861, B=70-317, C=318-564, D=2-69.
DR   PDB; 5BNP; X-ray; 2.15 A; A=565-861, B=70-317, C=318-564, D=2-69.
DR   PDB; 6HLN; X-ray; 2.10 A; B=1438-1497.
DR   PDB; 6HMV; X-ray; 2.24 A; B=1453-1497.
DR   PDBsum; 4WM7; -.
DR   PDBsum; 4WM8; -.
DR   PDBsum; 5BNN; -.
DR   PDBsum; 5BNO; -.
DR   PDBsum; 5BNP; -.
DR   PDBsum; 6HLN; -.
DR   PDBsum; 6HMV; -.
DR   SMR; Q68T42; -.
DR   MEROPS; C03.011; -.
DR   UniLectin; Q68T42; -.
DR   ABCD; Q68T42; 1 sequenced antibody.
DR   SABIO-RK; Q68T42; -.
DR   Proteomes; UP000105171; Genome.
DR   GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
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:0075509; P:endocytosis involved in viral entry into host cell; IEA:UniProtKB-KW.
DR   GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
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:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR   GO; GO:0018144; P:RNA-protein covalent cross-linking; IEA:UniProtKB-KW.
DR   GO; GO:0039554; P:suppression by virus of host MDA-5 activity; IEA:UniProtKB-KW.
DR   GO; GO:0039522; P:suppression by virus of host mRNA export from nucleus; IEA:UniProtKB-KW.
DR   GO; GO:0039644; P:suppression by virus of host NF-kappaB transcription factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0039722; P:suppression by virus of host toll-like receptor signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR   GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR   CDD; cd00205; rhv_like; 3.
DR   Gene3D; 2.40.10.10; -; 4.
DR   Gene3D; 2.60.120.20; -; 3.
DR   Gene3D; 3.30.70.270; -; 1.
DR   Gene3D; 6.10.20.20; -; 1.
DR   InterPro; IPR003593; AAA+_ATPase.
DR   InterPro; IPR043502; DNA/RNA_pol_sf.
DR   InterPro; IPR000605; Helicase_SF3_ssDNA/RNA_vir.
DR   InterPro; IPR014759; Helicase_SF3_ssRNA_vir.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR014838; P3A.
DR   InterPro; IPR036203; P3A_soluble_dom.
DR   InterPro; IPR044067; PCV_3C_PRO.
DR   InterPro; IPR000081; Peptidase_C3.
DR   InterPro; IPR000199; Peptidase_C3A/C3B_picornavir.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR003138; Pico_P1A.
DR   InterPro; IPR002527; Pico_P2B.
DR   InterPro; IPR001676; Picornavirus_capsid.
DR   InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR   InterPro; IPR033703; Rhv-like.
DR   InterPro; IPR001205; RNA-dir_pol_C.
DR   InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR   InterPro; IPR029053; Viral_coat.
DR   Pfam; PF08727; P3A; 1.
DR   Pfam; PF00548; Peptidase_C3; 1.
DR   Pfam; PF02226; Pico_P1A; 1.
DR   Pfam; PF00947; Pico_P2A; 1.
DR   Pfam; PF01552; Pico_P2B; 1.
DR   Pfam; PF00680; RdRP_1; 1.
DR   Pfam; PF00073; Rhv; 3.
DR   Pfam; PF00910; RNA_helicase; 1.
DR   SMART; SM00382; AAA; 1.
DR   SUPFAM; SSF50494; SSF50494; 2.
DR   SUPFAM; SSF52540; SSF52540; 1.
DR   SUPFAM; SSF56672; SSF56672; 1.
DR   SUPFAM; SSF89043; SSF89043; 1.
DR   PROSITE; PS51874; PCV_3C_PRO; 1.
DR   PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR   PROSITE; PS51218; SF3_HELICASE_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Activation of host autophagy by virus; ATP-binding;
KW   Autocatalytic cleavage; Capsid protein; Covalent protein-RNA linkage;
KW   Eukaryotic host gene expression shutoff by virus;
KW   Eukaryotic host translation shutoff by virus; Helicase; Host cytoplasm;
KW   Host cytoplasmic vesicle; Host gene expression shutoff by virus;
KW   Host membrane; Host mRNA suppression by virus; Host nucleus;
KW   Host-virus interaction; Hydrolase;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host MDA5 by virus;
KW   Inhibition of host mRNA nuclear export by virus;
KW   Inhibition of host NF-kappa-B by virus;
KW   Inhibition of host RLR pathway by virus;
KW   Inhibition of host TLR pathway by virus; Ion channel; Ion transport;
KW   Lipoprotein; Magnesium; Membrane; Metal-binding; Myristate;
KW   Nucleotide-binding; Nucleotidyltransferase; Phosphoprotein;
KW   Pore-mediated penetration of viral genome into host cell; Protease; Repeat;
KW   RNA-binding; RNA-directed RNA polymerase;
KW   T=pseudo3 icosahedral capsid protein; Thiol protease; Transferase;
KW   Transport; Viral attachment to host cell; Viral immunoevasion;
KW   Viral ion channel; Viral penetration into host cytoplasm;
KW   Viral RNA replication; Virion; Virus endocytosis by host;
KW   Virus entry into host cell; Zinc; Zinc-finger.
FT   INIT_MET        1
FT                   /note="Removed; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   CHAIN           2..2188
FT                   /note="Genome polyprotein"
FT                   /id="PRO_0000449051"
FT   CHAIN           2..861
FT                   /note="P1"
FT                   /id="PRO_0000449052"
FT   CHAIN           2..317
FT                   /note="Capsid protein VP0"
FT                   /id="PRO_0000449053"
FT   CHAIN           2..69
FT                   /note="Capsid protein VP4"
FT                   /id="PRO_0000449054"
FT   CHAIN           70..317
FT                   /note="Capsid protein VP2"
FT                   /id="PRO_0000449055"
FT   CHAIN           318..552
FT                   /note="Capsid protein VP3"
FT                   /id="PRO_0000449056"
FT   CHAIN           553..861
FT                   /note="Capsid protein VP1"
FT                   /id="PRO_0000449057"
FT   CHAIN           862..1437
FT                   /note="P2"
FT                   /id="PRO_0000449058"
FT   CHAIN           862..1008
FT                   /note="Protease 2A"
FT                   /id="PRO_0000449059"
FT   CHAIN           1009..1107
FT                   /note="Protein 2B"
FT                   /id="PRO_0000449060"
FT   CHAIN           1108..1437
FT                   /note="Protein 2C"
FT                   /id="PRO_0000449061"
FT   CHAIN           1438..2188
FT                   /note="P3"
FT                   /id="PRO_0000449062"
FT   CHAIN           1438..1548
FT                   /note="Protein 3AB"
FT                   /id="PRO_0000449063"
FT   CHAIN           1438..1526
FT                   /note="Protein 3A"
FT                   /id="PRO_0000449064"
FT   CHAIN           1527..1548
FT                   /note="Viral protein genome-linked"
FT                   /id="PRO_0000449065"
FT   CHAIN           1549..2188
FT                   /note="Protein 3CD"
FT                   /id="PRO_0000449066"
FT   CHAIN           1549..1731
FT                   /note="Protease 3C"
FT                   /id="PRO_0000449067"
FT   CHAIN           1732..2188
FT                   /note="RNA-directed RNA polymerase"
FT                   /id="PRO_0000449068"
FT   TOPO_DOM        2..1503
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        1504..1519
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1520..2188
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          1212..1370
FT                   /note="SF3 helicase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT   DOMAIN          1549..1727
FT                   /note="Peptidase C3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   DOMAIN          1954..2069
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   NP_BIND         1236..1243
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT   ZN_FING         1376..1394
FT                   /note="C4-type; degenerate"
FT                   /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT   REGION          1108..1246
FT                   /note="Oligomerization"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   REGION          1108..1180
FT                   /note="Membrane-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   REGION          1129..1133
FT                   /note="RNA-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   REGION          1421..1428
FT                   /note="RNA-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   REGION          1432..1437
FT                   /note="Oligomerization"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   ACT_SITE        879
FT                   /note="For protease 2A activity"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   ACT_SITE        897
FT                   /note="For protease 2A activity"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   ACT_SITE        968
FT                   /note="For protease 2A activity"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   ACT_SITE        1588
FT                   /note="For protease 3C activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   ACT_SITE        1619
FT                   /note="For protease 3C activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   ACT_SITE        1695
FT                   /note="For protease 3C activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT   METAL           914
FT                   /note="Zinc; structural"
FT                   /evidence="ECO:0000250|UniProtKB:Q9QF31"
FT   METAL           916
FT                   /note="Zinc; structural"
FT                   /evidence="ECO:0000250|UniProtKB:Q9QF31"
FT   METAL           974
FT                   /note="Zinc; structural"
FT                   /evidence="ECO:0000250|UniProtKB:Q9QF31"
FT   METAL           976
FT                   /note="Zinc; via pros nitrogen; structural"
FT                   /evidence="ECO:0000250|UniProtKB:Q9QF31"
FT   METAL           1376
FT                   /note="Zinc"
FT                   /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT   METAL           1389
FT                   /note="Zinc"
FT                   /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT   METAL           1394
FT                   /note="Zinc"
FT                   /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT   METAL           1960
FT                   /note="Magnesium 1; catalytic; for RdRp activity"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   METAL           1960
FT                   /note="Magnesium 2; catalytic; for RdRp activity"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   METAL           2055
FT                   /note="Magnesium 1; catalytic; for RdRp activity"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   METAL           2055
FT                   /note="Magnesium 2; catalytic; for RdRp activity"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   BINDING         408
FT                   /note="Sialic acid"
FT                   /evidence="ECO:0000269|PubMed:26563423"
FT   BINDING         412
FT                   /note="Sialic acid"
FT                   /evidence="ECO:0000269|PubMed:26563423"
FT   BINDING         548
FT                   /note="Sialic acid"
FT                   /evidence="ECO:0000269|PubMed:26563423"
FT   BINDING         549
FT                   /note="Sialic acid"
FT                   /evidence="ECO:0000269|PubMed:26563423"
FT   BINDING         550
FT                   /note="Sialic acid"
FT                   /evidence="ECO:0000269|PubMed:26563423"
FT   BINDING         834
FT                   /note="Sialic acid"
FT                   /evidence="ECO:0000269|PubMed:26563423"
FT   BINDING         838
FT                   /note="Sialic acid"
FT                   /evidence="ECO:0000269|PubMed:26563423"
FT   BINDING         839
FT                   /note="Sialic acid"
FT                   /evidence="ECO:0000269|PubMed:26563423"
FT   SITE            69..70
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   SITE            317..318
FT                   /note="Cleavage; by protease 3C"
FT                   /evidence="ECO:0000250|UniProtKB:P03301"
FT   SITE            861..862
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000250|UniProtKB:P03301"
FT   SITE            1008..1009
FT                   /note="Cleavage; by protease 3C"
FT                   /evidence="ECO:0000250|UniProtKB:P03301"
FT   SITE            1107..1108
FT                   /note="Cleavage; by protease 3C"
FT                   /evidence="ECO:0000250|UniProtKB:P03301"
FT   SITE            1132
FT                   /note="Involved in the interaction with host RTN3"
FT                   /evidence="ECO:0000250|UniProtKB:Q66478"
FT   SITE            1437..1438
FT                   /note="Cleavage; by protease 3C"
FT                   /evidence="ECO:0000250|UniProtKB:P03301"
FT   SITE            1526..1527
FT                   /note="Cleavage; by protease 3C"
FT                   /evidence="ECO:0000250|UniProtKB:P03301"
FT   SITE            1548..1549
FT                   /note="Cleavage; by protease 3C"
FT                   /evidence="ECO:0000250|UniProtKB:P03301"
FT   SITE            1731..1732
FT                   /note="Cleavage; by protease 3C"
FT                   /evidence="ECO:0000250|UniProtKB:P03301"
FT   MOD_RES         1529
FT                   /note="O-(5'-phospho-RNA)-tyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   LIPID           2
FT                   /note="N-myristoyl glycine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P03300"
FT   MUTAGEN         1460..1462
FT                   /note="NDL->AAA: Decreased recruitment of host PI4KB by the
FT                   complex protein 3A-ACBD3."
FT                   /evidence="ECO:0000269|PubMed:31381608"
FT   MUTAGEN         1469..1473
FT                   /note="QEVRD->AEVAA: Decreased recruitment of host PI4KB by
FT                   the complex protein 3A-ACBD3."
FT                   /evidence="ECO:0000269|PubMed:31381608"
FT   MUTAGEN         1481..1484
FT                   /note="IVIH->AAHA: Decreased recruitment of host PI4KB by
FT                   the complex protein 3A-ACBD3."
FT                   /evidence="ECO:0000269|PubMed:31381608"
FT   MUTAGEN         1489..1493
FT                   /note="LVVEK->AVAEA: Decreased recruitment of host PI4KB by
FT                   the complex protein 3A-ACBD3."
FT                   /evidence="ECO:0000269|PubMed:31381608"
FT   STRAND          33..35
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   HELIX           36..38
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   HELIX           51..54
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          57..59
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          63..65
FT                   /evidence="ECO:0007829|PDB:5BNP"
FT   STRAND          83..87
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          90..96
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   HELIX           103..105
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   TURN            113..115
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   HELIX           126..128
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          138..140
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          147..151
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   HELIX           153..155
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   HELIX           159..167
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          168..180
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          188..197
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          204..208
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   HELIX           212..215
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   HELIX           218..220
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   HELIX           227..229
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   TURN            230..233
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   HELIX           239..241
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          242..248
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   TURN            249..251
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          253..259
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          263..268
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   TURN            270..272
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          275..287
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          296..311
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   TURN            325..328
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          340..342
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   HELIX           360..362
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   TURN            363..365
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   HELIX           380..384
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          386..389
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          392..395
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          397..402
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          405..409
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   TURN            410..413
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   HELIX           415..420
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          423..428
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          430..436
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          445..451
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          453..455
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   HELIX           461..464
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          467..473
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          475..477
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          479..484
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          489..491
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   TURN            502..504
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          508..515
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          525..535
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   STRAND          540..544
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   HELIX           560..563
FT                   /evidence="ECO:0007829|PDB:4WM8"
FT   HELIX           593..595
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   HELIX           603..606
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   HELIX           619..621
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   HELIX           623..627
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          631..641
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          652..658
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   HELIX           665..671
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          674..691
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          706..712
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   HELIX           725..728
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          730..738
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          744..748
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          753..760
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          763..771
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   HELIX           777..779
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          783..788
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          797..815
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          825..827
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          835..840
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   STRAND          843..845
FT                   /evidence="ECO:0007829|PDB:5BNO"
FT   HELIX           1456..1466
FT                   /evidence="ECO:0007829|PDB:6HLN"
FT   HELIX           1469..1477
FT                   /evidence="ECO:0007829|PDB:6HLN"
FT   STRAND          1480..1483
FT                   /evidence="ECO:0007829|PDB:6HLN"
FT   HELIX           1486..1488
FT                   /evidence="ECO:0007829|PDB:6HLN"
FT   STRAND          1489..1494
FT                   /evidence="ECO:0007829|PDB:6HLN"
SQ   SEQUENCE   2188 AA;  243800 MW;  185C5A05E971727E CRC64;
     MGAQVTRQQT GTHENANIAT NGSHITYNQI NFYKDSYAAS ASKQDFSQDP SKFTEPVVEG
     LKAGAPVLKS PSAEACGYSD RVLQLKLGNS AIVTQEAANY CCAYGEWPNY LPDHEAVAID
     KPTQPETSTD RFYTLRSVKW ESNSTGWWWK LPDALNNIGM FGQNVQYHYL YRSGFLIHVQ
     CNATKFHQGA LLVVAIPEHQ RGAHDTTTSP GFNDIMKGER GGTFNHPYVL DDGTSIACAT
     IFPHQWINLR TNNSATIVLP WMNVAPMDFP LRHNQWTLAV IPVVPLGTRT MSSVVPITVS
     IAPMCCEFNG LRHAITQGVP TYLLPGSGQF LTTDDHSSAP VLPCFNPTPE MHIPGQIRNM
     LEMIQVESMM EINNTDGANG MERLRVDISV QADLDQLLFN IPLDIQLDGP LRNTLVGNIS
     RYYTHWSGSL EMTFMFCGSF MATGKLILCY TPPGGSCPTT RETAMLGTHI VWDFGLQSSI
     TLIIPWISGS HYRMFNSDAK STNANVGYVT CFMQTNLIVP SESSDTCSLI GFIAAKDDFS
     LRLMRDSPDI GQSNHLHGAE AAYQVESIIK TATDTVKSEI NAELGVVPSL NAVETGATSN
     TEPEEAIQTR TVINQHGVSE TLVENFLGRA ALVSKKSFEY KNHASSSAGT HKNFFKWTIN
     TKSFVQLRRK LELFTYLRFD AEITILTTVA VNGNNDSTYM GLPDLTLQAM FVPTGALTPK
     EQDSFHWQSG SNASVFFKIS DPPARMTIPF MCINSAYSVF YDGFAGFEKN GLYGINPADT
     IGNLCVRIVN EHQPVGFTVT VRVYMKPKHI KAWAPRPPRT MPYMSIANAN YKGRDTAPNT
     LNAIIGNRAS VTTMPHNIVT TGPGFGGVFV GSFKIINYHL ATIEERQSAI YVDWQSDVLV
     TPIAAHGRHQ IARCKCNTGV YYCRHRDRSY PICFEGPGIQ WIEQNEYYPA RYQTNVLLAA
     GPAEAGDCGG LLVCPHGVIG LLTAGGGGIV AFTDIRNLLW LDTDVMEQGI TDYIQNLGNA
     FGAGFTETIS NKAKEVQDML IGESSLLEKL LKALIKIISA LVIVIRNSED LITVTATLAL
     LGCHDSPWSY LKQKVCSYLG IPYVPRQSES WLKKFTEACN ALRGLDWLSQ KIDKFINWLK
     TKILPEAREK YEFVQRLKQL PVIEKQVSTI EHSCPTTERQ QALFNNVQYY SHYCRKYAPL
     YAVESKRVAA LEKKINNYIQ FKSKSRIEPV CLIIHGSPGT GKSVASNLIA RAITEKLGGD
     IYSLPPDPKY FDGYKQQTVV LMDDLMQNPD GNDISMFCQM VSTVDFIPPM ASLEEKGTLY
     TSPFLIATTN AGSIHAPTVS DSKALSRRFK FDVDIEVTDS YKDSNKLDMS RAVEMCKPDN
     CTPTNYKRCC PLICGKAIQF RDRRTNARST VDMLVTDIIK EYRTRNSTQD KLEALFQGPP
     QFKEIKISVA PDTPAPDAIN DLLRSVDSQE VRDYCQKKGW IVIHPSNELV VEKHISRAFI
     TLQAIATFVS IAGVVYVIYK LFAGIQGPYT GIPNPKPKVP SLRTAKVQGP GFDFAQAIMK
     KNTVIARTEK GEFTMLGVYD RVAVIPTHAS VGEIIYINDV ETRVLDACAL RDLTDTNLEI
     TIVKLDRNQK FRDIRHFLPR CEDDYNDAVL SVHTSKFPNM YIPVGQVTNY GFLNLGGTPT
     HRILMYNFPT RAGQCGGVVT TTGKVIGIHV GGNGAQGFAA MLLHSYFTDT QGEIVSNEKS
     GMCINAPAKT KLQPSVFHQV FEGSKEPAVL NSKDPRLKTD FEEAIFSKYT GNKIMLMDEY
     MEEAVDHYVG CLEPLDISVD PIPLENAMYG MEGLEALDLT TSAGFPYLLQ GKKKRDIFNR
     QTRDTSEMTK MLEKYGVDLP FVTFVKDELR SREKVEKGKS RLIEASSLND SVAMRVAFGN
     LYATFHNNPG TATGSAVGCD PDIFWSKIPI LLDGEIFAFD YTGYDASLSP VWFACLKKVL
     IKLGYTHQTS FIDYLCHSVH LYKDRKYVIN GGMPSGSSGT SIFNTMINNI IIRTLLIKVY
     KGIDLDQFKM IAYGDDVIAS YPHKIDPGLL AEAGKHYGLV MTPADKGTSF IDTNWENVTF
     LKRYFRADDQ YPFLIHPVMP MKEIHESIRW TKDPRNTQDH VRSLCYLAWH NGEEAYNEFC
     RKIRSVPVGR ALTLPAYSSL RRKWLDSF
//