Q66479 · POLG_HE71M

Function

function

Capsid protein VP1

Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity).
The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity).
Capsid protein VP1 mainly forms the vertices of the capsid (By similarity).
Capsid protein VP1, together with VP2, interacts with host cell receptor SCARB2 to provide virion attachment to target host cells (PubMed:30531980).
This attachment induces virion internalization (By similarity).
After binding to its receptor, the capsid undergoes conformational changes (By similarity).
Capsid protein VP1 N-terminus (that contains an amphipathic alpha-helix) and capsid protein VP4 are externalized (By similarity).
Together, they shape a pore in the host membrane through which viral genome is translocated to host cell cytoplasm (By similarity).

Capsid protein VP2

Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity).
The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity).
Capsid protein VP2, together with VP1, interacts with host cell receptor SCARB2 to provide virion attachment to target host cells (PubMed:30531980).

Capsid protein VP3

Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity).
The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity).

Capsid protein VP4

Lies on the inner surface of the capsid shell (By similarity).
After binding to the host receptor, the capsid undergoes conformational changes (By similarity).
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 (By similarity).

Capsid protein VP0

Component of immature procapsids, which is cleaved into capsid proteins VP4 and VP2 after maturation (By similarity).
Allows the capsid to remain inactive before the maturation step (By similarity).

Protease 2A

Cysteine protease that cleaves viral polyprotein and specific host proteins (By similarity).
It is responsible for the autocatalytic cleavage between the P1 and P2 regions, which is the first cleavage occurring in the polyprotein (By similarity).
Cleaves also the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA translation (By similarity).
Inhibits the host nucleus-cytoplasm protein and RNA trafficking by cleaving host members of the nuclear pores (By similarity).
Counteracts stress granule formation probably by antagonizing its assembly or promoting its dissassembly (By similarity).
Cleaves and inhibits host IFIH1/MDA5, thereby inhibiting the type-I IFN production and the establishment of the antiviral state (By similarity).
Cleaves and inhibits host MAVS, thereby inhibiting the type-I IFN production and the establishment of the antiviral state (By similarity).

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 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 3A

Localizes the viral replication complex to the surface of membranous vesicles (By similarity).
It inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport and causes the disassembly of the Golgi complex, possibly through GBF1 interaction (By similarity).
This would result in depletion of MHC, trail receptors and IFN receptors at the host cell surface (By similarity).
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 (Probable)

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 (By similarity).
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 (By similarity).
Following genome release from the infecting virion in the cytoplasm, the VPg-RNA linkage is probably removed by host TDP2 (By similarity).
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 (By similarity).

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.

Protease 3C

Major viral protease that mediates proteolytic processing of the polyprotein (By similarity).
Cleaves host EIF5B, contributing to host translation shutoff (By similarity).
Cleaves also host PABPC1, contributing to host translation shutoff (By similarity).
Disassembles host cytoplasmic stress granules by cleaving host G3BP1, although this effect is less prononced than the inhibition induced by protease 2A (By similarity).
Cleaves host RIGI and thus contributes to the inhibition of type I interferon production (By similarity).
Cleaves host IRF7 and thus contributes to the inhibition of type I interferon production (By similarity).
Cleaves host HNRNPA1 thereby increasing the translation of apoptosis protease activating factor APAF1, leading to apoptosis of the host cell (By similarity).
Cleaves host NLRP1, triggers host N-glycine-mediated degradation of the autoinhibitory NLRP1 N-terminal fragment (By similarity).

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.

Catalytic activity

Cofactor

RNA-directed RNA polymerase

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Note: Binds 2 magnesium ions that constitute a dinuclear catalytic metal center (By similarity).
The magnesium ions are not prebound but only present for catalysis (By similarity).
Requires the presence of 3CDpro or 3CPro (By similarity).

Activity regulation

RNA-directed RNA polymerase

Replication or transcription is subject to high level of random mutations by the nucleotide analog ribavirin.

Features

Showing features for site, active site, binding site.

TypeIDPosition(s)Description
Site69-70Cleavage; by autolysis
Site323-324Cleavage; by protease 3C
Site862-863Cleavage; by autolysis
Active site883For protease 2A activity
Active site901For protease 2A activity
Binding site918Zn2+ 1 (UniProtKB | ChEBI); structural
Binding site920Zn2+ 1 (UniProtKB | ChEBI); structural
Active site972For protease 2A activity
Binding site978Zn2+ 1 (UniProtKB | ChEBI); structural
Binding site980Zn2+ 1 (UniProtKB | ChEBI); structural
Site1012-1013Cleavage; by protease 3C
Site1111-1112Cleavage; by protease 3C
Site1136Involved in the interaction with host RTN3
Binding site1240-1247ATP (UniProtKB | ChEBI)
Binding site1381Zn2+ 2 (UniProtKB | ChEBI)
Binding site1392Zn2+ 2 (UniProtKB | ChEBI)
Binding site1397Zn2+ 2 (UniProtKB | ChEBI)
Site1440-1441Cleavage; by protease 3C
Site1526-1527Cleavage; by protease 3C
Site1548-1549Cleavage; by protease 3C
Active site1588For protease 3C activity
Active site1619For protease 3C activity
Active site1695For protease 3C activity
Site1731-1732Cleavage; by protease 3C
Binding site1964Mg2+ 1 (UniProtKB | ChEBI); catalytic; for RdRp activity
Binding site1964Mg2+ 2 (UniProtKB | ChEBI); catalytic; for RdRp activity
Binding site2060Mg2+ 1 (UniProtKB | ChEBI); catalytic; for RdRp activity
Binding site2060Mg2+ 2 (UniProtKB | ChEBI); catalytic; for RdRp activity

GO annotations

AspectTerm
Cellular Componenthost cell cytoplasmic vesicle membrane
Cellular Componenthost cell nucleus
Cellular Componentmembrane
Cellular ComponentT=pseudo3 icosahedral viral capsid
Molecular FunctionATP binding
Molecular Functionchannel activity
Molecular Functioncysteine-type endopeptidase activity
Molecular Functionmetal ion binding
Molecular Functionribonucleoside triphosphate phosphatase activity
Molecular FunctionRNA binding
Molecular FunctionRNA helicase activity
Molecular FunctionRNA-dependent RNA polymerase activity
Molecular Functionstructural molecule activity
Biological Processclathrin-dependent endocytosis of virus by host cell
Biological ProcessDNA replication
Biological ProcessDNA-templated transcription
Biological Processentry receptor-mediated virion attachment to 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 MAVS activity
Biological Processsymbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity
Biological Processsymbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity
Biological Processsymbiont-mediated suppression of host mRNA export from nucleus
Biological Processviral RNA genome replication
Biological Processvirus-mediated perturbation of host defense response

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

Organism names

Accessions

  • Primary accession
    Q66479

Proteomes

Subcellular Location

Capsid protein VP0

Capsid protein VP4

Capsid protein VP2

Virion

Capsid protein VP3

Virion

Capsid protein VP1

Virion

Protein 2B

Host cytoplasmic vesicle membrane
; Peripheral membrane protein
Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.

Protein 2C

Host cytoplasmic vesicle membrane
; Peripheral membrane protein
Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.

Protein 3A

Host cytoplasmic vesicle membrane
; Peripheral membrane protein
Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.

Protein 3AB

Host cytoplasmic vesicle membrane
; Peripheral membrane protein
Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.

Viral protein genome-linked

Virion
Host cytoplasm

Protease 3C

Protein 3CD

Host nucleus
Host cytoplasm
Host cytoplasmic vesicle membrane
; Peripheral membrane protein
Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.

RNA-directed RNA polymerase

Host cytoplasmic vesicle membrane
; Peripheral membrane protein
Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.

Features

Showing features for topological domain, intramembrane.

TypeIDPosition(s)Description
Topological domain2-1503Cytoplasmic
Intramembrane1504-1519
Topological domain1520-2193Cytoplasmic

Keywords

PTM/Processing

Features

Showing features for initiator methionine, lipidation, chain, modified residue.

TypeIDPosition(s)Description
Initiator methionine1Removed; by host
Lipidation2N-myristoyl glycine; by host
ChainPRO_00004261532-69Capsid protein VP4
ChainPRO_00004261522-323Capsid protein VP0
ChainPRO_00004261512-862P1
ChainPRO_00004261502-2193Genome polyprotein
ChainPRO_000042615470-323Capsid protein VP2
ChainPRO_0000426155324-565Capsid protein VP3
ChainPRO_0000426156566-862Capsid protein VP1
ChainPRO_0000039496863-1012Protease 2A
ChainPRO_0000426157863-1440P2
ChainPRO_00000394971013-1111Protein 2B
ChainPRO_00000394981112-1440Protein 2C
ChainPRO_00000394991441-1526Protein 3A
ChainPRO_00004261591441-1548Protein 3AB
ChainPRO_00004261581441-2193P3
ChainPRO_00004261601527-1548Viral protein genome-linked
Modified residue1529O-(5'-phospho-RNA)-tyrosine
ChainPRO_00004261621549-1731Protease 3C
ChainPRO_00004261611549-2193Protein 3CD
ChainPRO_00004261631732-2193RNA-directed RNA polymerase

Post-translational modification

Genome polyprotein

Specific enzymatic cleavages in vivo by the viral proteases yield processing intermediates and the mature proteins.

Capsid protein VP0

Myristoylation is required for the formation of pentamers during virus assembly. Further assembly of 12 pentamers and a molecule of genomic RNA generates the provirion.

Capsid protein VP0

During virion maturation, immature virions are rendered infectious following cleavage of VP0 into VP4 and VP2. This maturation seems to be an autocatalytic event triggered by the presence of RNA in the capsid and it is followed by a conformational change infectious virion.

Capsid protein VP4

Myristoylation is required during RNA encapsidation and formation of the mature virus particle.

Viral protein genome-linked

VPg is uridylylated by the polymerase into VPg-pUpU. This acts as a nucleotide-peptide primer for the genomic RNA replication.

Keywords

Interaction

Subunit

Capsid protein VP0

Interacts with capsid protein VP1 and capsid protein VP3 to form heterotrimeric protomers.

Capsid protein VP1

Interacts with capsid protein VP0, and capsid protein VP3 to form heterotrimeric protomers (By similarity).
Five protomers subsequently associate to form pentamers which serve as building blocks for the capsid (By similarity).
Interacts with capsid protein VP2, capsid protein VP3 and capsid protein VP4 following cleavage of capsid protein VP0 (By similarity).
Interacts with host SCARB2 (PubMed:30531980).
Interacts with host ARF6; this interaction mediates viral endocytosis (By similarity).

Capsid protein VP2

Interacts with capsid protein VP1 and capsid protein VP3 in the mature capsid (By similarity).
Interacts with host SCARB2 (PubMed:30531980).

Capsid protein VP3

Interacts with capsid protein VP0 and capsid protein VP1 to form heterotrimeric protomers (By similarity).
Five protomers subsequently associate to form pentamers which serve as building blocks for the capsid (By similarity).
Interacts with capsid protein VP4 in the mature capsid (By similarity).
Interacts with protein 2C; this interaction may be important for virion morphogenesis (By similarity).

Capsid protein VP4

Interacts with capsid protein VP1 and capsid protein VP3.

Protease 2A

Homodimer.

Protein 2B

Interacts with host BAX; this interaction activates the mitochondrial apoptotic pathway. Interacts with host ILF2.

Protein 2C

Homohexamer; forms a hexameric ring structure with 6-fold symmetry characteristic of AAA+ ATPases (By similarity).
Interacts (via N-terminus) with host RTN3 (via reticulon domain); this interaction is important for viral replication (By similarity).
Interacts with capsid protein VP3; this interaction may be important for virion morphogenesis (By similarity).

Protein 3AB

Interacts with protein 3CD.

Protein 3A

Homodimer (By similarity).
Interacts with host GBF1 (By similarity).
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 (PubMed:31381608).

Viral protein genome-linked

Interacts with RNA-directed RNA polymerase.

Protease 3C

Interacts with host IFIH1/MDA5; this interaction inhibits host IFIH1.

Protein 3CD

Interacts with protein 3AB and with RNA-directed RNA polymerase.

RNA-directed RNA polymerase

Interacts with Viral protein genome-linked and with protein 3CD.

Family & Domains

Features

Showing features for region, domain, zinc finger.

TypeIDPosition(s)Description
Region1-22Disordered
Region568-588Amphipathic alpha-helix
Domain1216-1374SF3 helicase
Zinc finger1381-1397C4-type; degenerate
Domain1549-1727Peptidase C3
Domain1958-2073RdRp catalytic

Domain

Protein 2C

The N-terminus has membrane-binding (By similarity).
The N-terminus also displays RNA-binding properties (By similarity).
The N-terminus is involved in oligomerization (By similarity).
The central part contains an ATPase domain and a degenerate C4-type zinc-finger with only 3 cysteines (By similarity).
The C-terminus is involved in RNA-binding (By similarity).
The extreme C-terminus contains a region involved in oligomerization (By similarity).

Sequence similarities

Belongs to the picornaviruses polyprotein family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    2,193
  • Mass (Da)
    242,657
  • Last updated
    2007-01-23 v3
  • Checksum
    35E1B3CFF88A50EF
MGSQVSTQRSGSHENSNSATEGSTINYTTINYYKDSYAATAGKQSLKQDPDKFANPVKDIFTEMAAPLKSPSAEACGYSDRVAQLTIGNSTITTQEAANIIVGYGEWPSYCSDDDATAVDKPTRPDVSVNRFYTLDTKLWEKSSKGWYWKFPDVLTETGVFGQNAQFHYLYRSGFCIHVQCNASKFHQGALLVAILPEYVIGTVAGGTGTEDSHPPYKQTQPGADGFELQHPYVLDAGIPISQLTVCPHQWINLRTNNCATIIVPYMNTLPFDSALNHCNFGLLVVPISPLDFDQGATPVIPITITLAPMCSEFGGLRQAVTQGFPTELKPGTNQFLTTDDGVSAPILPNFHPTPCIHIPGEVRNLLELCQVETILEVNNVPTNATSLMERLRFPVSAQAGKGELCAVFRADPGRDGPWQSTMLGQLCGYYTQWSGSLEVTFMFTGSFMATGKMLIAYTPPGGPLPKDRATAMLGTHVIWDFGLQSSVTLVIPWISNTHYRAHARDGVFDYYTTGLVSIWYQTNYVVPIGAPNTAYILALAAAQKNFTMKLCKDTSHILQTASIQGDRVADVIESSIGDSVSRALTQALPAPTGQNTQVSSHRLDTGEVPALQAAEIGASSNTSDESMIETRCVLNSHSTAETTLDSFFSRAGLVGEIDLPLEGTTNPNGYANWDIDITGYAQMRRKVELFTYMRFDAEFTFVACTPTGEVVPQLLQYMFVPPGAPKPESRESLAWQTATNPSVFVKLTDPPAQVSVPFMSPASAYQWFYDGYPTFGEHKQEKDLEYGACPNNMMGTFSVRTVGSSKSKYPLVVRIYMRMKHVRAWIPRPMRNQNYLFKANPNYAGNSIKPTGTSRNAITTLGKFGQQSGAIYVGNFRVVNRHLATHNDWANLVWEDSSRDLLVSSTTAQGCDTIARCNCQTGVYYCNSKRKHYPVSFSKPSLIYVEASEYYPARYQSHLMLAAGHSESGDCGGILRCQHGVVGIASTGGNGLVGFADVRDLLWLDEEAMEQGVSDYIKGLGDAFGTGFTDAVSREVEALRNHLIGSDGAVEKILKNLIKLISALVIVIRSDYDMVTLTATLALIGCHGSPWAWIKAKTASILGIPIAQKQSASWLKKFNDMASAAKGLEWISNKISKFIDWLREKIVPAAKEKAEFLTNLKQFPLLENQITHLEQSAASQEDLEAMFGNVSYLAHFCRKFQPLYATEAKRVYVLEKRMNNYMQFKSTHRIEPVCLIIRGSPGTGKSLATGIIARAIADKYHSSVYSLPPDPDHFDGYKQQVVTVMDDLCQNPDGKDMSLFYQMVSTVDIIPPMASLEEKGVSFTSKFVIASTNASNIIVPTVSDSDAIRRRFYMDCDIEVTDSSKTDLGRLDAGRAAKLCSENNTANFKRCSPLVCGKAIQLRDRKSKVRYSVDTVVSELIREYNSRSAIGNTIEALFQGPPKFRPIRISLEEKPAPDAISDLLASVDSEEVRQYCREQGWIIPETPTNVERHLNRAVLVMQSIATVVAVVSLVYVIYKLFAGFQGAYSGAPNQVLKKPVLRTATVQGPSLDFALSLLRRNIRQVQTDQGHFTMLGVRDRLAVLPRHSQPGKTIWVEHKLVNILDAAELVDEQGVNLELTLVTLDTNEKFRDITKFIPETISGASDATLVINTEHMPSMFVPVGDVVQYGFLNLSGKPTHRTMMYNFPTKAGQCGGVVTSVGKIIGIHIGGNGRQGFCAGLKRSYFASEQGEIQWVKSNKETGRLNINGPTRTKLEPSVFHDVFEANKEPAVLTSKDPRLEVDFEQALFSKYVGNVLHEPDEYVHQAALHYANQLKQLDINTKKMSMEEACYGTDNLEAIDLHTSAGYPYSALGIKKRDILDPATRDVSKMKSYMDKYGLDLPYSTYVKDELRSLDKIKKGKSRLIEASSLNDSVYLRMTFGHLYEVFHANPGTVTGSAVGCNPDVFWSKLPILLPGSLFAFDYSGYDASLSPVWFRALEVVLREIGYSEEAVSLIEGINHTHHIYRNKTYCVLGGMPSGCSGTSIFNSMINNIIIRTLLIKTFKGIDLDELNMVAYGDDVLASYPFPIDCLELAKTGKEYGLTMTPAGKSPCFNEVTWENATFLKRGFLPDHQFPFLIHPTMPMKEIHESIRWTKDARNTQDHVRSLCLLAWHNGKDEYEKFVSTIRSVPVGKALAIPNFENLRRNWLELF

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U22522
EMBL· GenBank· DDBJ
AAB39969.1
EMBL· GenBank· DDBJ
Genomic RNA

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