POLG_HED68
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 03-AUG-2022, entry version 146.
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]
RP FUNCTION (PROTEASE 2A), AND MUTAGENESIS OF CYS-968.
RX PubMed=33148796; DOI=10.1128/jvi.01856-20;
RA Kang J., Pang Z., Zhou Z., Li X., Liu S., Cheng J., Liu P., Tan W.,
RA Wang Z., Wang T.;
RT "Enterovirus D68 Protease 2Apro Targets TRAF3 To Subvert Host Innate Immune
RT Responses.";
RL J. Virol. 95:0-0(2021).
RN [7] {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 [8] {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 [9] {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). Also plays a role in the suppression of host innate
CC immunity through cleavage of host TRAF3, a component of the signaling
CC cascade required to produce type I interferons (PubMed:33148796).
CC {ECO:0000250|UniProtKB:P03300, ECO:0000269|PubMed:30867299,
CC ECO:0000269|PubMed:33148796}.
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:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0018144; P:RNA-protein covalent cross-linking; IEA:UniProtKB-KW.
DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW.
DR GO; GO:0039522; P:suppression by virus of host mRNA export from nucleus; IEA:UniProtKB-KW.
DR GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; IEA:UniProtKB-KW.
DR GO; GO:0039722; P:suppression by virus of host toll-like receptor signaling pathway; 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: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 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 BINDING 408
FT /ligand="N-acetylneuraminate"
FT /ligand_id="ChEBI:CHEBI:35418"
FT /evidence="ECO:0000269|PubMed:26563423"
FT BINDING 412
FT /ligand="N-acetylneuraminate"
FT /ligand_id="ChEBI:CHEBI:35418"
FT /evidence="ECO:0000269|PubMed:26563423"
FT BINDING 548
FT /ligand="N-acetylneuraminate"
FT /ligand_id="ChEBI:CHEBI:35418"
FT /evidence="ECO:0000269|PubMed:26563423"
FT BINDING 549
FT /ligand="N-acetylneuraminate"
FT /ligand_id="ChEBI:CHEBI:35418"
FT /evidence="ECO:0000269|PubMed:26563423"
FT BINDING 550
FT /ligand="N-acetylneuraminate"
FT /ligand_id="ChEBI:CHEBI:35418"
FT /evidence="ECO:0000269|PubMed:26563423"
FT BINDING 834
FT /ligand="N-acetylneuraminate"
FT /ligand_id="ChEBI:CHEBI:35418"
FT /evidence="ECO:0000269|PubMed:26563423"
FT BINDING 838
FT /ligand="N-acetylneuraminate"
FT /ligand_id="ChEBI:CHEBI:35418"
FT /evidence="ECO:0000269|PubMed:26563423"
FT BINDING 839
FT /ligand="N-acetylneuraminate"
FT /ligand_id="ChEBI:CHEBI:35418"
FT /evidence="ECO:0000269|PubMed:26563423"
FT BINDING 914
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 916
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 974
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 976
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 1236..1243
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT BINDING 1376
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT BINDING 1389
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT BINDING 1394
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:B9VUU3"
FT BINDING 1960
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 1960
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:P03300"
FT BINDING 2055
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 2055
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 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 968
FT /note="C->A: Loss of cleavage activity on host TRAF3."
FT /evidence="ECO:0000269|PubMed:33148796"
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
