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Protein

Genome polyprotein

Gene
N/A
Organism
Enterovirus A71
Status
Unreviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.UniRule annotation
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.UniRule annotation
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.UniRule annotation
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.UniRule annotation
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. After genome has been released, the channel shrinks.UniRule annotation
Protease 3C: cleaves host DDX58/RIG-I and thus contributes to the inhibition of type I interferon production. Cleaves also host PABPC1.UniRule annotation
Protein 2A: Cysteine protease that cleaves viral polyprotein and specific host proteins. It is responsible for the cleavage between the P1 and P2 regions, 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.UniRule annotation
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 cyctoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication.UniRule annotation
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.UniRule annotation
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 dissassembly 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.UniRule annotation
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.UniRule annotation
Protein 3CD: Is 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. The 3C domain in the context of protein 3CD may have an RNA binding activity.UniRule annotation
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.UniRule annotation
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. VPg may be removed in the cytoplasm by an unknown enzyme termed "unlinkase". VPg is not cleaved off virion genomes because replicated genomic RNA are encapsidated at the site of replication.UniRule annotation

Catalytic activityi

NTP + H2O = NDP + phosphate.UniRule annotationSAAS annotation
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).UniRule annotationSAAS annotation
Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.UniRule annotationSAAS annotation
Selective cleavage of Tyr-|-Gly bond in the picornavirus polyprotein.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi136Calcium 1Combined sources1
Metal bindingi153Calcium 2Combined sources1
Metal bindingi217Calcium 2Combined sources1
Metal bindingi225Calcium 1Combined sources1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHelicaseUniRule annotationSAAS annotation, Hydrolase, Ion channel, Nucleotidyltransferase, Protease, RNA-bindingUniRule annotationSAAS annotation, RNA-directed RNA polymeraseUniRule annotationSAAS annotation, Thiol proteaseSAAS annotation, Transferase, Viral ion channelUniRule annotationSAAS annotation
Biological processActivation of host autophagy by virusUniRule annotation, Eukaryotic host gene expression shutoff by virus, Eukaryotic host translation shutoff by virusUniRule annotation, Host gene expression shutoff by virus, Host mRNA suppression by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host mRNA nuclear export by virusUniRule annotation, Inhibition of host RIG-I by virusUniRule annotation, Inhibition of host RLR pathway by virus, Ion transport, Pore-mediated penetration of viral genome into host cellUniRule annotation, Transport, Viral attachment to host cellUniRule annotationSAAS annotation, Viral immunoevasion, Viral penetration into host cytoplasm, Viral RNA replicationUniRule annotationSAAS annotation, Virus endocytosis by hostUniRule annotation, Virus entry into host cell
LigandATP-binding, CalciumCombined sources, Metal-bindingCombined sources, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Genome polyproteinUniRule annotation
Cleaved into the following 17 chains:
P3UniRule annotation
Protein 3ABUniRule annotation
P2UniRule annotation
P1UniRule annotation
Capsid protein VP0UniRule annotation
Alternative name(s):
VP4-VP2UniRule annotation
Capsid protein VP4UniRule annotation
Alternative name(s):
P1AUniRule annotation
Virion protein 4UniRule annotation
Capsid protein VP2UniRule annotation
Alternative name(s):
P1BUniRule annotation
Virion protein 2UniRule annotation
Capsid protein VP3UniRule annotation
Alternative name(s):
P1CUniRule annotation
Virion protein 3UniRule annotation
Capsid protein VP1UniRule annotation
Alternative name(s):
P1DUniRule annotation
Virion protein 1UniRule annotation
Protease 2AUniRule annotation (EC:3.4.22.29UniRule annotation)
Short name:
P2AUniRule annotation
Alternative name(s):
Picornain 2AUniRule annotation
Protein 2AUniRule annotation
Protein 2BUniRule annotation
Short name:
P2BUniRule annotation
Protein 2CUniRule annotation (EC:3.6.1.15UniRule annotation)
Short name:
P2CUniRule annotation
Protein 3AUniRule annotation
Short name:
P3AUniRule annotation
Viral protein genome-linkedUniRule annotation
Short name:
VPgUniRule annotation
Alternative name(s):
Protein 3BUniRule annotation
Short name:
P3BUniRule annotation
Protein 3CDUniRule annotation (EC:3.4.22.28UniRule annotation)
Protease 3CUniRule annotation
Short name:
P3CUniRule annotation
RNA-directed RNA polymeraseUniRule annotation (EC:2.7.7.48UniRule annotation)
Short name:
RdRpUniRule annotation
Alternative name(s):
3D polymeraseUniRule annotation
Short name:
3DpolUniRule annotation
Protein 3DUniRule annotation
Short name:
3DUniRule annotation
OrganismiEnterovirus A71Imported
Taxonomic identifieri39054 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA positive-strand viruses, no DNA stagePicornaviralesPicornaviridaeEnterovirusEnterovirus A
Proteomesi
  • UP000101185 Componenti: Genome

Subcellular locationi

  • Host cytoplasmic vesicle membrane SAAS annotation; Peripheral membrane protein SAAS annotation; Cytoplasmic side SAAS annotation
  • Virion SAAS annotation

GO - Cellular componenti

Keywords - Cellular componenti

Capsid protein, Host cytoplasmUniRule annotationSAAS annotation, Host cytoplasmic vesicleUniRule annotationSAAS annotation, Host membraneUniRule annotationSAAS annotation, Membrane, T=pseudo3 icosahedral capsid proteinUniRule annotation, Virion

PTM / Processingi

Keywords - PTMi

Covalent protein-RNA linkageUniRule annotation, Lipoprotein, MyristateUniRule annotation

Interactioni

Subunit structurei

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 VP4 in the mature capsid (By similarity). Capsid protein VP0: interacts with capsid protein VP1 and capsid protein VP3 to form heterotrimeric protomers. Five protomers subsequently associate to form pentamers which serve as building blocks for the capsid. Capsid protein VP2: Interacts with capsid protein VP1 and capsid protein VP3 in the mature capsid (By similarity). Capsid protein VP3: 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 (By similarity). Capsid protein VP4: Interacts with capsid protein VP1 and capsid protein VP3 (By similarity). Protein 2C: interacts with capsid protein VP3; this interaction may be important for virion morphogenesis (By similarity). Protein 3AB: interacts with protein 3CD (By similarity). Viral protein genome-linked: interacts with RNA-directed RNA polymerase (By similarity). 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.UniRule annotation

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3ZFEX-ray2.70A566-863[»]
B70-323[»]
C324-565[»]
D1-69[»]
3ZFFX-ray3.40A566-862[»]
B70-323[»]
C324-565[»]
D1-69[»]
3ZFGX-ray3.20A566-863[»]
B70-323[»]
C324-565[»]
D1-69[»]
4AEDX-ray3.80A566-862[»]
B70-323[»]
C324-565[»]
D1-69[»]
4C0Uelectron microscopy10.00A566-863[»]
B70-323[»]
C324-565[»]
4C0Yelectron microscopy16.00A566-863[»]
B70-323[»]
C324-565[»]
4C10electron microscopy13.00A566-863[»]
B70-323[»]
C324-565[»]
D1-69[»]
ProteinModelPortaliA9X4C2.
SMRiA9X4C2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1216 – 1374SF3 helicaseInterPro annotationAdd BLAST159
Domaini1958 – 2073RdRp catalyticInterPro annotationAdd BLAST116

Sequence similaritiesi

Belongs to the picornaviruses polyprotein family.UniRule annotationSAAS annotation

Keywords - Domaini

RepeatUniRule annotation

Family and domain databases

CDDicd00205. rhv_like. 3 hits.
Gene3Di4.10.80.10. 1 hit.
InterProiView protein in InterPro
IPR003593. AAA+_ATPase.
IPR000605. Helicase_SF3_ssDNA/RNA_vir.
IPR014759. Helicase_SF3_ssRNA_vir.
IPR027417. P-loop_NTPase.
IPR014838. P3A.
IPR036203. P3A_soluble_dom.
IPR000081. Peptidase_C3.
IPR000199. Peptidase_C3A/C3B_picornavir.
IPR009003. Peptidase_S1_PA.
IPR003138. Pico_P1A.
IPR036988. Pico_P1A_sf.
IPR002527. Pico_P2B.
IPR001676. Picornavirus_capsid.
IPR033703. Rhv-like.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
PfamiView protein in Pfam
PF08727. P3A. 1 hit.
PF00548. Peptidase_C3. 1 hit.
PF02226. Pico_P1A. 1 hit.
PF00947. Pico_P2A. 1 hit.
PF01552. Pico_P2B. 1 hit.
PF00680. RdRP_1. 1 hit.
PF00073. Rhv. 3 hits.
PF00910. RNA_helicase. 1 hit.
ProDomiView protein in ProDom or Entries sharing at least one domain
PD001306. Peptidase_C3. 1 hit.
PD649346. Pico_P2B. 1 hit.
SMARTiView protein in SMART
SM00382. AAA. 1 hit.
SUPFAMiSSF50494. SSF50494. 2 hits.
SSF52540. SSF52540. 1 hit.
SSF89043. SSF89043. 1 hit.
PROSITEiView protein in PROSITE
PS50507. RDRP_SSRNA_POS. 1 hit.
PS51218. SF3_HELICASE_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

A9X4C2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSQVSTQRS GSHENSNSAT EGSTINYTTI NYYKDSYAAT AGKQSLKQDP
60 70 80 90 100
DKFANPVKDI FTEMAAPLKS PSAEACGYSD RVAQLTIGNS TITTQEAANI
110 120 130 140 150
IVGYGEWPSY CSDDDATAVD KPTRPDVSVN RFYTLDTKLW EKSSKGWYWK
160 170 180 190 200
FPDVLTETGV FGQNAQFHYL YRSGFCIHVQ CNASKFHQGA LLVAILPEYV
210 220 230 240 250
IGTVAGGTGT EDSHPPYKQT QPGADGFELQ HPYVLDAGIP ISQLTVCPHQ
260 270 280 290 300
WINLRTNNCA TIIVPYMNTL PFDSALNHCN FGLLVVPISP LDFDQGATPV
310 320 330 340 350
IPITITLAPM CSEFAGLRQA VTQGFPTEPK PGTNQFLTTD DGVSAPILPN
360 370 380 390 400
FHPTPCIHIP GEVRNLLELC QVETILEVNN VPTNATSLME RLRFPVSAQA
410 420 430 440 450
GKGELCAVFR ADPGRDGPWQ STMLGQLCGY YTQWSGSLEV TFMFTGSFMA
460 470 480 490 500
TGKMLIAYTP PGGPLPKDRA TAMLGTHVIW DFGLQSSVTL VIPWISNTHY
510 520 530 540 550
RAHARDGVFD YYTTGLVSIW YQTNYVVPIG APNTAYIIAL AAAQKNFTMK
560 570 580 590 600
LCKDTSHILQ TASIQGDRVA DVIESSIGDS VSRALTQALP APTGQNTQVS
610 620 630 640 650
SHRLDTGEVP ALQAAEIGAS SNTSDESMIE TRCVLNSHST AETTLDSFFS
660 670 680 690 700
RAGLVGEIDL PLEGTTNPNG YANWDIDITG YAQMRRKVEL FTYMRFDAEF
710 720 730 740 750
TFVACTPTGQ VVPQLLQYMF VPPGAPKPES RESLAWQTAT NPSVFVKLTD
760 770 780 790 800
PPAQVSVPFM SPASAYQWFY DGYPTFGEHK QEKDLEYGAC PNNMMGTFSV
810 820 830 840 850
RNVGSSKSKY PLVVRIYMRM KHVRAWIPRP MRNQNYLFKA NPNYAGNSIK
860 870 880 890 900
PTGTSRTAIT TLGKFGQQSG AIYVGNFRVV NRHLATHNDW ANLVWEDSSR
910 920 930 940 950
DLLVSSTTAQ GCDTIARCDC QTGVYYCNSK RKHYPVSFSK PSLIYVEASE
960 970 980 990 1000
YYPARYQSHL MLAAGHSEPG DCGGILRCQH GVVGIVSTGG NGLVGFADVR
1010 1020 1030 1040 1050
DLLWLDEEAM EQGVSDYIKG LGDAFGTGFT DAVSREVEAL KNHLIGSEGA
1060 1070 1080 1090 1100
VEKILKNLIK LISALVIVIR SDYDMVTLTA TLALIGCHGS PWAWIKAKTA
1110 1120 1130 1140 1150
SILGIPIAQK QSASWLKKFN DMANAAKGLE WISSKISKFI DWLKEKIIPA
1160 1170 1180 1190 1200
AREKVEFLNN LKQLPLLENQ ISNLEQSAAS QEDLEAMFGN VSYLAHFCRK
1210 1220 1230 1240 1250
FQPLYATEAK RVYALEKRMN NYMQFKSKHR IEPVCLIIRG SPGTGKSLAT
1260 1270 1280 1290 1300
GIIARAIADK YHSSVYSLPP DPDHFDGYKQ QVVTVMDDLC QNPDGKDMSL
1310 1320 1330 1340 1350
FCQMVSTVDF IPPMASLEEK GVSFTSKFVI ASTNSSNIIV PTVSDSDAIR
1360 1370 1380 1390 1400
RRFYMDCDIE VTDSYKTDLG RLDAGRAAKL CSENNTANFK RCSPLVCGKA
1410 1420 1430 1440 1450
IQLRDRKSKV RYSVDTVVSE LIREYNNRSA IGNTIEALFQ GPPKFRPIRI
1460 1470 1480 1490 1500
SLEEKPAPDA ISDLLASVDS EEVRQYCRDQ GWIIPETPTN VERHLNRAVL
1510 1520 1530 1540 1550
VMQSIATVVA VVSLVYVIYK LFAGFQGAYS GAPKQILKKP VLRTATVQGP
1560 1570 1580 1590 1600
SLDFALSLLR RNIRQVQTDQ GHFTMLGVRD RLAVLPRHSQ PGKTIWVEHK
1610 1620 1630 1640 1650
LVNILDAVEL VDEQGVNLEL TLITLDTNEK FRDITKFIPE SISAASDATL
1660 1670 1680 1690 1700
VINTEHMPSM FVPVGDVVQY GFLNLSGKPT HRTMMYNFPT KAGQCGGVVT
1710 1720 1730 1740 1750
SVGKVIGIHI GGNGRQGFCA GLKRSYFASE QGEIQWVKPN KETGRLNING
1760 1770 1780 1790 1800
PTRTKLEPSV FHDVFEGNKE PAVLHSKDPR LEVDFEQALF SKYVGNTLYE
1810 1820 1830 1840 1850
PDEYIKEAAL HYANQLKQLD IDTSQMSMEE ACYGTENLEA IDLHTSAGYP
1860 1870 1880 1890 1900
YSALGIKKRD ILDSTTRDVS KMKFYMDKYG LDLPYSTYVK DELRSIDKIK
1910 1920 1930 1940 1950
KGKSRLIEAS SLNDSVYLRM TFGHLYETFH ANPGTVTGSA VGCNPDTFWS
1960 1970 1980 1990 2000
KLPILLPGSL FAFDYSGYDA SLSPVWFRAL ELVLREIGYS EEAVSLVEGI
2010 2020 2030 2040 2050
NHTHHVYRNK TYCVLGGMPS GCSGTSIFNS MINNIIIRAL LIKTFKGIDL
2060 2070 2080 2090 2100
DELNMVAYGD DVLASYPFPI DCLELARTGK EYGLTMTPAD KSPCFNEVNW
2110 2120 2130 2140 2150
DNVTFLKRGF LPDEQFPFLI HPTMPMKEIH ESIRWTKDAR NTQDHVRSLC
2160 2170 2180 2190
LLAWHNGKQE YEKFVSAIRS VPVGKALAIP NYENLRRNWL ELF
Length:2,193
Mass (Da):242,982
Last modified:February 5, 2008 - v1
Checksum:iF07DD434AE01FB4A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ341368 Genomic RNA. Translation: ABC69262.1.

Similar proteinsi

Entry informationi

Entry nameiA9X4C2_9ENTO
AccessioniPrimary (citable) accession number: A9X4C2
Entry historyiIntegrated into UniProtKB/TrEMBL: February 5, 2008
Last sequence update: February 5, 2008
Last modified: November 22, 2017
This is version 85 of the entry and version 1 of the sequence. See complete history.
Entry statusiUnreviewed (UniProtKB/TrEMBL)

Miscellaneousi

Keywords - Technical termi

3D-structureCombined sources, Complete proteomeImported