A0A2K9Y515 · A0A2K9Y515_HED68

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 (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
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.
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
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 Processsymbiont genome entry into host cell via pore formation in plasma membrane
Biological Processsymbiont-mediated suppression of host innate immune response
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
  • Strain
    • NY586_17
  • Taxonomic lineage
    Viruses > Riboviria > Orthornavirae > Pisuviricota > Pisoniviricetes > Picornavirales > Picornaviridae > Ensavirinae > Enterovirus > Enterovirus D

Accessions

  • Primary accession
    A0A2K9Y515

Subcellular Location

Cytoplasmic vesicle membrane
; Peripheral membrane protein
Host cytoplasmic vesicle membrane
; Peripheral membrane protein
Host nucleus
Membrane
; Peripheral membrane protein
Virion

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.
Interacts with RNA-directed RNA polymerase.
Interacts with capsid protein VP1 and capsid protein VP3 to form heterotrimeric protomers.
Interacts with protein 3CD.

Structure

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain1213-1371SF3 helicase
Domain1550-1728Peptidase C3
Domain1955-2070RdRp catalytic

Sequence similarities

Belongs to the picornaviruses polyprotein family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    2,189
  • Mass (Da)
    243,975
  • Last updated
    2018-04-25 v1
  • Checksum
    B3A74C09861569A2
MGAQVTRQQTGTHENANIATNGSHITYNQINFYKDSYAASASKQDFSQDPSKFTEPVVEGLKAGAPVLKSPSAEACGYSDRVLQLKLGNSAIVTQEAANYCCAYGEWPNYLPDHEAVAIDKPTQPETATDRFYTLKSVKWETESTGWWWKLPDALNNIGMFGQNVQHHYLYRSGFLIHVQCNATKFHQGALLVVAIPEHQRGAHNTTTSPGFDDIMKGEEGGTFNHPYVLDDGTSLACATIFPHQWINLRTNNSATIVLPWMNAAPMDFPLRHNQWTLAVIPVVPLGTRTVSSMVPITVSIAPMCCEFNGLRHAIAQGVPTYLLPGSGQFLTTDDHSSAPVLPCFNPTPEMHIPGQVRNMLEVIQVESMMEINNTETAVGMQRLKVDISVLTDVDQLLFNIPLDIQLDGPLRNTLVGNISRYYTHWSGSLEMTFMFCGSFMATGKLILCYTPPGGSCPTTRETAMLGTHVVWDFGLQSSVTLVIPWISGSHYRMFNNDAKSTNANVGYVTCFMQTNLIVPNESSNTCSLIGFVAAKDDFSLRLMRDSPDIGQLEHLHEAEAAYQIESIIKTATDTVKSEINAELGVVPSLNAVETGASSNTEPEEAIQTRTVINQHGVSETLVENFLSRAALVSKRSFEYKNHTSSEARVDKNFYKWTINTKSFVQLRRKLELFTYLRFDAEITILTTVAVGSNNSTYMGLPDLTLQAMFVPTGALTPEKQDSFHWQSGSNASVFFKVSDPPARMTIPFMCINSAYSVFYDGFAGFEKNGLYGINPADTIGNLCVRIVNEHQPIGFTVTVRVYMKPKHIKAWAPRPPRTLPYMSIANANYKGKERAPNALNAIIGNRESIKTMPHDIRLVNTGPGFGGVFVGSFKIINYHLATTEERQSAIYVDWQSDVLVTPIAAHGRHQIARCKCNTGVYYCRHRDKSYPVCFEGPGIQWIEQNEYYPARYQTNVLLAAGPAEAGDCGGLLVCPHGVIGLLTAGGGGIVAFTDIRNLLWLDTDAMEQGITDYIQNLGNAFGAGFTETISSKAKEVQDMLIGESSLLEKLLKALIKIISALVIVIRNSEDLVTVTATLALLGCHDSPWSYLKQKVCSYLGIPYVPRQSESWLKKFTEACNALRGLDWLSQKIDKFISWLKNKILPEAREKYEFVQRLKQLPVIESQVSTIEHSCPTTEQQQALFNNVQYYSHYCKKYAPLYAVEAKRVTALEKKINNYIQFKSKSRIEPVCLIIHGSPGTGKSVASNLIARAITEKLGGDVYSLPPDPKYFDGYKQQTVVLMDDLMQNPDGNDISMFCQMVSTVDFIPPMASLEEKGTLYTSPFLIATTNAGSIHAPTVSDSKALSRRFKFDVDIEVTDSYKDSNKLDMSRAVEMCKPDDCAPTNYKRCCPLICGKAIQFRDRRTNARSTIDMLVTDIIKEYRIRNSTQDKLEALFQGPPQFKEIKISVTPDTPAPDAINDLLRSVDSQEVRDYCQKKGWIVIHPSNELVVEKHISRAFITLQAVATFVSIAGVVYVIYKLFAGIQGPYTGIPNPKPKVPSLRTAKVQGPGFDFAQAIMKKNTVIARTEKGEFTMLGIHDRVAVIPTHASVGEIIYINDVETKVLDACALRDLTDTNLEITIVKLDRNQKFRDIRHFLPRYEDDYNDAVLSVHTSKFPNMYIPVGQVTNYGFLNLGGTPTHRILMYNFPTRAGQCGGVVTTTGKVIGIHVGGNGAQGFAAMLLHSYFTDTQGEIVSNEKSGVCINGPAKTKLQPSVFHQVFEGSKEPAVLNSKDPRLKTDFEEAVFSKYTGNKIMLMDEYMEEAVDHYVGCLEPLDISIDPIPLESAMYGMDGLEALDLTTSAGFPYLLQGKKKRDIFNRQTRDTTEMTRMLEKYGVDLPFVTFVKDELRSREKVEKGKSRLIEASSLNDSVAMRVAFGNLYATFHNNPGTATGSAVGCDPDIFWSKIPILLDGEIFAFDYTGYDASLSPVWFACLKKVLIKLGYTHQTSFIDYLCHSVHLYKDRKYIVNGGMPSGSSGTSIFNTMINNIIIRTLLIRVYKGIDLDQFKMIAYGDDVIASYPHKIDPGLLAEAGKHYGLLMTPADKGTSFVDTNWENVTFLKRYFRADDQYPFLVHPVMPMKEIHESIRWTKDPRNTQDHVRSLCYLAWHNGEEAYNEFCRKIRSVPVGRALTLPAYSSLRRKWLDSF

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
MG757146
EMBL· GenBank· DDBJ
AUW27286.1
EMBL· GenBank· DDBJ
Genomic RNA

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp