A0A7G1DCX5 · A0A7G1DCX5_9ENTO

  • Protein
    Genome polyprotein
  • Status
    UniProtKB unreviewed (TrEMBL)
  • Amino acids
  • Protein existence
    Inferred from homology
  • Annotation score
    5/5

Function

function

Acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU. The oriI viral genomic sequence may act as a template for this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome. Following genome release from the infecting virion in the cytoplasm, the VPg-RNA linkage is probably removed by host TDP2. During the late stage of the replication cycle, host TDP2 is excluded from sites of viral RNA synthesis and encapsidation, allowing for the generation of progeny virions.
Capsid protein VP0: Component of immature procapsids, which is cleaved into capsid proteins VP4 and VP2 after maturation. Allows the capsid to remain inactive before the maturation step.
Capsid protein VP1: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome. Capsid protein VP1 mainly forms the vertices of the capsid. Capsid protein VP1 interacts with host cell receptor to provide virion attachment to target host cells. This attachment induces virion internalization. Tyrosine kinases are probably involved in the entry process. After binding to its receptor, the capsid undergoes conformational changes. Capsid protein VP1 N-terminus (that contains an amphipathic alpha-helix) and capsid protein VP4 are externalized. Together, they shape a pore in the host membrane through which viral genome is translocated to host cell cytoplasm. After genome has been released, the channel shrinks.
Capsid protein VP2: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome.
Capsid protein VP3: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome.
Capsid protein VP4: Lies on the inner surface of the capsid shell. After binding to the host receptor, the capsid undergoes conformational changes. Capsid protein VP4 is released, Capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm.
Cysteine protease that cleaves viral polyprotein and specific host proteins. It is responsible for the autocatalytic cleavage between the P1 and P2 regions, which is the first cleavage occurring in the polyprotein. Cleaves also the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA translation. Inhibits the host nucleus-cytoplasm protein and RNA trafficking by cleaving host members of the nuclear pores. Counteracts stress granule formation probably by antagonizing its assembly or promoting its dissassembly. Cleaves and inhibits host IFIH1/MDA5, thereby inhibiting the type-I IFN production and the establishment of the antiviral state. Cleaves and inhibits host MAVS, thereby inhibiting the type-I IFN production and the establishment of the antiviral state.
Localizes the viral replication complex to the surface of membranous vesicles. It inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport and causes the disassembly of the Golgi complex, possibly through GBF1 interaction. This would result in depletion of MHC, trail receptors and IFN receptors at the host cell surface. Plays an essential role in viral RNA replication by recruiting ACBD3 and PI4KB at the viral replication sites, thereby allowing the formation of the rearranged membranous structures where viral replication takes place.
Protease 2A: Cysteine protease that cleaves viral polyprotein and specific host proteins.
Protease 3C: Major viral protease that mediates proteolytic processing of the polyprotein. Cleaves host EIF5B, contributing to host translation shutoff. Cleaves also host PABPC1, contributing to host translation shutoff.
Protein 2B: Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication.
Protein 2C: Induces and associates with structural rearrangements of intracellular membranes. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3.
Protein 3A: Localizes the viral replication complex to the surface of membranous vesicles. It inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport and causes the disassembly of the Golgi complex, possibly through GBF1 interaction. This would result in depletion of MHC, trail receptors and IFN receptors at the host cell surface.
Protein 3AB: Localizes the viral replication complex to the surface of membranous vesicles. Together with protein 3CD binds the Cis-Active RNA Element (CRE) which is involved in RNA synthesis initiation. Acts as a cofactor to stimulate the activity of 3D polymerase, maybe through a nucleid acid chaperone activity.
Protein 3CD: Involved in the viral replication complex and viral polypeptide maturation. It exhibits protease activity with a specificity and catalytic efficiency that is different from protease 3C. Protein 3CD lacks polymerase activity. Protein 3CD binds to the 5'UTR of the viral genome.
RNA-directed RNA polymerase: Replicates the viral genomic RNA on the surface of intracellular membranes. May form linear arrays of subunits that propagate along a strong head-to-tail interaction called interface-I. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss+RNA genomes are either translated, replicated or encapsidated.
Viral protein genome-linked: acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU. The oriI viral genomic sequence may act as a template for this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome.

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

GO annotations

AspectTerm
Cellular Componentcytoplasmic vesicle membrane
Cellular Componenthost cell cytoplasmic vesicle membrane
Cellular Componenthost cell nucleus
Cellular ComponentT=pseudo3 icosahedral viral capsid
Molecular FunctionATP binding
Molecular FunctionATP hydrolysis activity
Molecular Functionchannel activity
Molecular Functioncysteine-type endopeptidase activity
Molecular Functionmetal ion binding
Molecular FunctionRNA binding
Molecular FunctionRNA helicase activity
Molecular FunctionRNA-dependent RNA polymerase activity
Molecular Functionstructural molecule activity
Biological ProcessDNA-templated transcription
Biological Processendocytosis involved in viral entry into host cell
Biological Processinduction by virus of host autophagy
Biological Processmonoatomic ion transmembrane transport
Biological Processproteolysis
Biological ProcessRNA-protein covalent cross-linking
Biological Processsymbiont genome entry into host cell via pore formation in plasma membrane
Biological Processsymbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity
Biological Processsymbiont-mediated suppression of host mRNA export from nucleus
Biological Processviral RNA genome replication
Biological Processvirion attachment to host cell
Biological Processvirus-mediated perturbation of host defense response

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Genome polyprotein
  • Cleaved into 17 chains
    • P3
    • Protein 3AB
    • P2
    • P1
    • Capsid protein VP0
      Alternative names: VP4-VP2

Organism names

  • Taxonomic identifier
  • Organism
  • Strain
    • HK436180/2012
  • Taxonomic lineage
    Viruses > Riboviria > Orthornavirae > Pisuviricota > Pisoniviricetes > Picornavirales > Picornaviridae > Ensavirinae > Enterovirus > Enterovirus A

Accessions

  • Primary accession
    A0A7G1DCX5

Subcellular Location

Keywords

PTM/Processing

Keywords

Interaction

Subunit

Capsid protein VP1: Interacts with capsid protein VP0, and capsid protein VP3 to form heterotrimeric protomers. Five protomers subsequently associate to form pentamers which serve as building blocks for the capsid. Interacts with capsid protein VP2, capsid protein VP3 and capsid protein VP4 following cleavage of capsid protein VP0.
Homodimer. Interacts with host GBF1. Interacts (via GOLD domain) with host ACBD3 (via GOLD domain); this interaction allows the formation of a viral protein 3A/ACBD3 heterotetramer with a 2:2 stoichiometry, which will stimulate the recruitment of host PI4KB in order to synthesize PI4P at the viral RNA replication sites.
Homohexamer; forms a hexameric ring structure with 6-fold symmetry characteristic of AAA+ ATPases. Interacts (via N-terminus) with host RTN3 (via reticulon domain); this interaction is important for viral replication. Interacts with capsid protein VP3; this interaction may be important for virion morphogenesis.
Interacts with RNA-directed RNA polymerase.
Interacts with capsid protein VP0 and capsid protein VP1 to form heterotrimeric protomers. Five protomers subsequently associate to form pentamers which serve as building blocks for the capsid. Interacts with capsid protein VP4 in the mature capsid. Interacts with protein 2C; this interaction may be important for virion morphogenesis.
Interacts with capsid protein VP1 and capsid protein VP3 to form heterotrimeric protomers.
Interacts with protein 3CD.

Family & Domains

Features

Showing features for region, domain.

Type
IDPosition(s)Description
Region1-20Disordered
Domain1224-1382SF3 helicase
Domain1557-1735Peptidase C3
Domain1966-2081RdRp catalytic

Sequence similarities

Belongs to the picornaviruses polyprotein family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    2,201
  • Mass (Da)
    244,287
  • Last updated
    2021-02-10 v1
  • Checksum
    BE3599F176B74F99
MGAQVSTQRSGSHETSTVAREGSTINFTNINYYKDSYAASGSKQDYSQDPSKFTQPVMDVLKEMAPPLQSPSAEACGYSDRVAQLTVGNSTITTQEAANIVVGYGEWPNYCPDTDATAVDKPTRPDVSVNRFYTLSTKSWTQNSKGWYWKFPDVLNDVGVFGQNAQYHYLYRSGFCVHVQCNASKFHQGALLVAMVPEFVIASKSERSKPNDPAQYPAFSVTNPGKSGREFTDPYVLDAGIPLSQALIFPHQWINLRTNNCATIIMPYINAVPFDSAINHNNCGLVVVPVAPLKYSAGATTEIPITITIAPLNSEFSGLRQAVKQGIPVEMKPGTNQFLTTDDGVSAPILPGFDPTPVVHIPGEVSSILELCQVETILEVNNVTDVQGVSRLLIPVKAQETVDTLCASFQVDPGRDGPWQSTLIGQLCRYYTQWSGSLEITFMFTGSFMATGKMLIAYTPPGSAQPTTRELAMLGTHIIWDFGLQSSVTLVVPWISNTHFRTVKTGGYLDYYATGVVTIWYQTNFVVPPDTPNEANIIAMGAGQKNFTLKLCKDTPEITQQAVLQGDAIADAIQNTVTSTIQKVTTNVVGQDATAANTAPSSHSLNTGLVPALQAAETGASSTATDGNLIETRCVVNSNGTRETHIEHFFSRSGLVGVMEVDDTGTAGKGFSNWDIDIMAFVQLRRKLEAFTYMRFDAEFTFVTNLENGLTNNSVIQYMYVPPGAPKPDARESFQWQTATNPSVFQKMDSPPPQVSVPFMSPASAYQWFYDGYPTFGPHSETSNLSYGQCPNNMLGTFSARVVSKQITNQKFQIRIYLRLKRVRAWVPRPLRSQPYIYRNYPTYGTTIQHLAKDRRKITETDYNAEQRTHGKFGQQSGAVYVGNFRVVNRHLATHNDWANLVWEDSSRDLLVSSTTAQGCDTIARCNCQTGVYYCNSKRKHYPVSFSKPSLIYVEASEYYPARYQSHLMLAEGHSEPGDCGGILRCQHGVVGIVSTGGNGLVGFADIRDLLWLDEEAMEQGVSDYIKGLGDAFGTGFTDAVSREVEALKNYLIGSEGAVEKVLKNLVKLISALVIVIRSDYDMVTLTATLALIGCHGSPWAWIKAKTASILGIPIAQKQSASWLKKFNDMANAAKGLEWISNKISKFIDWLKEKIIPAAREKVEFLNNLKQLPLLENQISNLEQSAASQEDLEVMFGNVSYLAHFCRKLQPLYATEAKRVYALEKRMNNYMQFKSKHRIEPVCLIIRGSPGTGKSLATGIIARAIADKYHSSVYSLPPDPDHFDGYKQQVVTVMDDLCQNPDGKDMSLFCQMVSTVDFIPPMASLEEKGVSFTSKFVIASTNASNIIVPTVSDSDAIRRRFYMDCDIEVTDSYKTDLGRLDAGRAAKLCSENNTANFKRCSPLVCGKAIQLRDRKTKVRYSVDTVISELIREYNNRSAIGNTIEALFQGPPKFRPIRISLEETPAPDAISDLLASVDSEEVRQYCRDQGWIIPETPTNVERHLNRAVLVMQSIATVVAVVSLVYVIYKLFAGFQGAYSGAPKQALKKPVLRTATVQGPSLDFALSLLRRNIRQVQTDQGHFTMLGVRDRLAVLPRHSQPGKTIWVEHKLVNVLDAVELVDEQGVNLELTLITLDTNEKFRDITKFIPEGISGASDATLVINTEHMPSMFVPVGDVVQYGFLNLSGKPTHRTMMYNFPTKAGQCGGVVTSVGKVIGIHIGGNGRQGFCAGLKRSYFASEQGEIQWVKPNKETGRLNINGPTRTKLEPSVFHDVFEGNKEPAVLHNKDPRLEVDFEQALFSKYVGNTLHEPDEYIREAALHYANQLKQLNINTSQMSMEEACYGTEDLEAIDLHTSAGYPYSALGIKKRDILDPITRDVSKMKFYMDKYGLDLPYSTYVKDELRSIDKIKKGKSRLIEASSLNDSVYLRMAFGHLYETFHANPGTVTGSAVGCNPDVFWSKLPILLPGSLFAFDYSGYDASLSPVWFRALEMVLREIGYSEEAISLIEGINHTHHVYRNKTYCVLGGMPSGCSGTSIFNSMINNIIIRALLIKTFKGIDLDELNMVAYGDDVLASYPFPIDCLELAKTGKEYGLTMTPADKSPCFNEVNWENATFLKRGFLPDDQFPFLIHPTMPMKEIHESIRWTKDARNTQDHVRSLCLLAWHNGKQEYEKFVSTIRSVPVGKALAIPNYENLRRNWLELF

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
MH780724
EMBL· GenBank· DDBJ
AYI50396.1
EMBL· GenBank· DDBJ
Genomic RNA

Similar Proteins

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