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Protein

Genome polyprotein

Gene
N/A
Organism
Human hepatitis A virus genotype IIA (isolate CF-53) (HHAV) (Human hepatitis A virus (isolate Human/France/CF-53/1979))
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Protein inferred from homologyi

Functioni

Capsid proteins VP1, VP2, and VP3 form a closed capsid enclosing the viral positive strand RNA genome. All these proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with HAVCR1 to provide virion attachment to target cell (By similarity).By similarity
Protein VP0: VP0 precursor is a component of immature procapsids. The N-terminal domain of VP0, protein VP4, is needed for the assembly of 12 pentamers into the icosahedral structure. Unlike other picornaviruses, HAV VP4 does not seem to be myristoylated and has not been detected in mature virions, supposedly owing to its small size (By similarity).By similarity
VP1-2A precursor is a component of immature procapsids and corresponds to an extended form of the structural protein VP1. The C-terminal domain of VP1-2A, protein 2A, acts as an assembly signal that allows multimerization of VP1-2A and formation of pentamers of VP1-VP2-VP3 trimers. It is proteolytically removed from the precursor by a host protease and does not seem to be found in mature particles (By similarity).By similarity
Protein 2B and 2BC precursor affect membrane integrity and cause an increase in membrane permeability.By similarity
Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).By similarity
Protein 3A, via its hydrophobic domain, serves as membrane anchor to the 3AB and 3ABC precursors.By similarity
The 3AB precursor interacts with the 3CD precursor and with RNA structures found at both the 5'- and 3'-termini of the viral genome. Since the 3AB precursor contains the hydrophobic domain 3A, it probably anchors the whole viral replicase complex to intracellular membranes on which viral RNA synthesis occurs (By similarity).By similarity
The 3ABC precursor is targeted to the mitochondrial membrane where protease 3C activity cleaves and inhibits the host antiviral protein MAVS, thereby disrupting activation of IRF3 through the IFIH1/MDA5 pathway. In vivo, the protease activity of 3ABC precursor is more efficient in cleaving the 2BC precursor than that of protein 3C. The 3ABC precursor may therefore play a role in the proteolytic processing of the polyprotein (By similarity).By similarity
Protein 3B is covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. It acts as a genome-linked replication primer (By similarity).By similarity
Protease 3C: cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease. Also cleaves host proteins such as PCBP2 (By similarity).By similarity
RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals.PROSITE-ProRule annotation

Catalytic activityi

Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).PROSITE-ProRule 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.
NTP + H2O = NDP + phosphate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei769Important for VP1 folding and capsid assemblyBy similarity1
Active sitei1561For protease 3C activityBy similarity1
Active sitei1601For protease 3C activityBy similarity1
Active sitei1689For protease 3C activityBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1230 – 1237ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Helicase, Hydrolase, Ion channel, Nucleotidyltransferase, Protease, RNA-directed RNA polymerase, Thiol protease, Transferase, Viral ion channel

Keywords - Biological processi

Eukaryotic host gene expression shutoff by virus, Eukaryotic host translation shutoff by virus, Host gene expression shutoff by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host MAVS by virus, Inhibition of host RLR pathway by virus, Interferon antiviral system evasion, Ion transport, Transport, Viral attachment to host cell, Viral immunoevasion, Viral RNA replication, Virus entry into host cell

Keywords - Ligandi

ATP-binding, Nucleotide-binding, RNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Genome polyprotein
Cleaved into the following 18 chains:
Alternative name(s):
VP4-VP2
Alternative name(s):
P1A
Virion protein 4
Alternative name(s):
P1B
Virion protein 2
Alternative name(s):
P1C
Virion protein 3
Alternative name(s):
PX
Alternative name(s):
P1D
Virion protein 1
Protein 2A
Short name:
P2A
Protein 2B
Short name:
P2B
Protein 2C (EC:3.6.1.15)
Short name:
P2C
Protein 3ABCD
Short name:
P3
Protein 3A
Short name:
P3A
Protein 3B
Short name:
P3B
Alternative name(s):
VPg
Protease 3C (EC:3.4.22.28)
Short name:
P3C
Alternative name(s):
Picornain 3C
OrganismiHuman hepatitis A virus genotype IIA (isolate CF-53) (HHAV) (Human hepatitis A virus (isolate Human/France/CF-53/1979))
Taxonomic identifieri470591 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA positive-strand viruses, no DNA stagePicornaviralesPicornaviridaeHepatovirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000007899 Componenti: Genome

Subcellular locationi

Protein VP2 :
Protein VP3 :
Protein VP1 :
Protein VP1-2A :
Protein 2B :
Protein 2C :
  • Host cytoplasmic vesicle membrane Curated; Peripheral membrane protein Curated; Cytoplasmic side Curated

  • 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. May associate with membranes through a N-terminal amphipathic helix (By similarity).By similarity
Protein 3ABC :
Protein 3AB :
Protein 3A :
Protein 3B :
RNA-directed RNA polymerase 3D-POL :
  • Host cytoplasmic vesicle membrane Curated; Peripheral membrane protein Curated; Cytoplasmic side Curated

  • Note: Interacts with membranes in a complex with viral protein 3AB. 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 (By similarity).By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 1465CytoplasmicSequence analysisAdd BLAST1465
Intramembranei1466 – 1480Sequence analysisAdd BLAST15
Topological domaini1481 – 2225CytoplasmicSequence analysisAdd BLAST745

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Capsid protein, Host cytoplasm, Host cytoplasmic vesicle, Host membrane, Host mitochondrion, Host mitochondrion outer membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003105991 – 2225Genome polyproteinAdd BLAST2225
ChainiPRO_00003106001 – 245Protein VP0Sequence analysisAdd BLAST245
ChainiPRO_00003106011 – 23Protein VP4Sequence analysisAdd BLAST23
ChainiPRO_000031060224 – 245Protein VP2Sequence analysisAdd BLAST222
ChainiPRO_0000310603246 – 491Protein VP3Sequence analysisAdd BLAST246
ChainiPRO_0000310604492 – 836Protein VP1-2ASequence analysisAdd BLAST345
ChainiPRO_0000310605492 – 769Protein VP1Sequence analysisAdd BLAST278
ChainiPRO_0000310606770 – 836Protein 2ASequence analysisAdd BLAST67
ChainiPRO_0000310607837 – 1422Protein 2BCSequence analysisAdd BLAST586
ChainiPRO_0000310608837 – 1087Protein 2BSequence analysisAdd BLAST251
ChainiPRO_00003106091088 – 1422Protein 2CSequence analysisAdd BLAST335
ChainiPRO_00003106101423 – 2225Protein 3ABCDSequence analysisAdd BLAST803
ChainiPRO_00003106111423 – 1736Protein 3ABCSequence analysisAdd BLAST314
ChainiPRO_00003106121423 – 1517Protein 3ABSequence analysisAdd BLAST95
ChainiPRO_00003106131423 – 1494Protein 3ASequence analysisAdd BLAST72
ChainiPRO_00003106141495 – 1517Protein 3BSequence analysisAdd BLAST23
ChainiPRO_00003106151518 – 2225Protein 3CDSequence analysisAdd BLAST708
ChainiPRO_00003106161518 – 1736Protease 3CSequence analysisAdd BLAST219
ChainiPRO_00003106171737 – 2225RNA-directed RNA polymerase 3D-POLSequence analysisAdd BLAST489

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1497O-(5'-phospho-RNA)-tyrosineBy similarity1

Post-translational modificationi

Specific enzymatic cleavages by the viral protease in vivo yield a variety of precursors and mature proteins. Polyprotein processing intermediates are produced, such as P1-2A which is a functional precursor of the structural proteins, VP0 which is a VP4-VP2 precursor, VP1-2A precursor, 3ABC precursor which is a stable and catalytically active precursor of 3A, 3B and 3C proteins, 3AB and 3CD precursors. The assembly signal 2A is removed from VP1-2A by a host protease. During virion maturation, non-infectious particles are rendered infectious following cleavage of VP0. This maturation cleavage is followed by a conformational change of the particle (By similarity).By similarity
VPg is uridylylated by the polymerase and is covalently linked to the 5'-end of genomic RNA. This uridylylated form acts as a nucleotide-peptide primer for the polymerase (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei23 – 24CleavageSequence analysis2
Sitei245 – 246Cleavage; by protease 3CSequence analysis2
Sitei491 – 492Cleavage; by protease 3CSequence analysis2
Sitei769 – 770Cleavage; by hostSequence analysis2
Sitei836 – 837Cleavage; by protease 3CBy similarity2
Sitei1087 – 1088Cleavage; by protease 3CSequence analysis2
Sitei1422 – 1423Cleavage; by protease 3CSequence analysis2
Sitei1494 – 1495Cleavage; by protease 3CSequence analysis2
Sitei1517 – 1518Cleavage; by protease 3CSequence analysis2
Sitei1736 – 1737Cleavage; by protease 3CBy similarity2

Keywords - PTMi

Covalent protein-RNA linkage, Phosphoprotein

Interactioni

Subunit structurei

3AB precursor is a homodimer. 3AB precursor interacts with 3CD precursor. Protein 3ABC interacts with human MAVS (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ5Y944.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1204 – 1366SF3 helicasePROSITE-ProRule annotationAdd BLAST163
Domaini1518 – 1714Peptidase C3Add BLAST197
Domaini1974 – 2095RdRp catalyticPROSITE-ProRule annotationAdd BLAST122

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili1127 – 1152Sequence analysisAdd BLAST26

Sequence similaritiesi

Belongs to the picornaviridae polyprotein family.Curated
Contains 1 peptidase C3 domain.Curated
Contains 1 RdRp catalytic domain.PROSITE-ProRule annotation
Contains 1 SF3 helicase domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Family and domain databases

CDDicd00205. rhv_like. 2 hits.
Gene3Di2.60.120.20. 3 hits.
InterProiIPR004004. Helic/Pol/Pept_Calicivir-typ.
IPR000605. Helicase_SF3_ssDNA/RNA_vir.
IPR014759. Helicase_SF3_ssRNA_vir.
IPR024354. Hepatitis_A_VP1-2A.
IPR027417. P-loop_NTPase.
IPR000199. Peptidase_C3A/C3B_picornavir.
IPR009003. Peptidase_S1_PA.
IPR001676. Picornavirus_capsid.
IPR033703. Rhv-like.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR029053. Viral_coat.
[Graphical view]
PfamiPF12944. HAV_VP. 1 hit.
PF00548. Peptidase_C3. 1 hit.
PF00680. RdRP_1. 1 hit.
PF00073. Rhv. 2 hits.
PF00910. RNA_helicase. 1 hit.
[Graphical view]
PRINTSiPR00918. CALICVIRUSNS.
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS50507. RDRP_SSRNA_POS. 1 hit.
PS51218. SF3_HELICASE_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q5Y944-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNMSRQGIFQ TVGSGLDHIL SLADIEEEQM IQSVDRTAVT GASYFTSVDQ
60 70 80 90 100
SSVHTAEVGS HQIEPLKTSV DKPGSKKTQG EKFFLIHSAD WLTTHALFHE
110 120 130 140 150
VAKLDVVKLL YNEQFAVQGL LRYHTYARFG IEIQVQINPT PFQQGGLICA
160 170 180 190 200
MVPGDQSYGS IASLTVYPHG LLNCNINNVV RIKVPFIYTR GAYHFKDPQY
210 220 230 240 250
PVWELTIRVW SELNIGTGTS AYTSLNVLAR FTDLELHGLT PLSTQMMRNE
260 270 280 290 300
FRVSTTENVV NLSNYEDARA KMSFALDQED WKSDPSQGGG IKITHFTTWT
310 320 330 340 350
SIPTLAAQFP FNASDSVGQQ IKVIPVDPYF FQMTNSNPDQ KCITALASIC
360 370 380 390 400
QMFCFWRGDL VFDFQVFPTK YHSGRLLFCF VPGNELIDVS GITLKQATTA
410 420 430 440 450
PCAVMDIAGV QSTLRFRVPW IPDTRYRVNR YTKSAHQKGE YTAIGKLIVY
460 470 480 490 500
CYNRLTSPSN VASHVRVNVY LSAINLECFA PLYHAMDVTT QVGDDSGGFS
510 520 530 540 550
TTVSTEQNVP DPQVGITTMR DLKGKANRGK MDVSGVQAPV GAITTIEDPV
560 570 580 590 600
LAKKVPETFP ELKPGESRHT SDHMSIYKFM GRSHFLCTFT FNSNNKEYTF
610 620 630 640 650
PITLSSTSNP PHGLPSTLRW FFNLFQLYRG PLDLTIIITG ATDVDGMAWF
660 670 680 690 700
TPVGLAVDTP WVEKESALSI DYKTALGAVR FNTRRTGNIQ IRLPWYSYLY
710 720 730 740 750
AVSGALDGLG DKTDSTFGLV SIQIANYNHS DEYLSFSCYL SVTEQSEFYF
760 770 780 790 800
PRAPLNSNAM LSTETMMSRI AAGDLESSVD DPRSEEDRRF ESHIESRKPY
810 820 830 840 850
KELRLEVGKQ RLKYAQEELS NEVLPPPRKM KGLFSQAKIS LFYTEEHEIM
860 870 880 890 900
KFSWRGVTAD TRALRRFGFS LAAGRSVWTL EMDAGVLTGR LVRLNDEKWT
910 920 930 940 950
EMKDDKIVSL VEKFTSNKHW SKVNFPHGML DLEEIAANSK DFPNMSETDL
960 970 980 990 1000
CFLLHWLNPK KINLADRMLG LSGVQEIKEQ GIGLIAECRT FLDSITGSLK
1010 1020 1030 1040 1050
SMMFGFHHSV TVDIVNIVLC FVKSGILLYV IQQLNQDEHS HIIGLLRVMN
1060 1070 1080 1090 1100
YADIGCSVIS CGKVFSKMLE TVFNWQMDSR MMELRTQSFS NWLRDICSGI
1110 1120 1130 1140 1150
TIFKSFKDAI YWLYTKLKDF YDMNYGKKKD VLNVLKDNQQ RIERAIEEAD
1160 1170 1180 1190 1200
NFCMLQIQDV EKFEQFQKGV DLIQKLRTVH SMAQVDSSLM IHLSPLRDCI
1210 1220 1230 1240 1250
ARVHQKLKNL GSINQAMVTR CEPVVCYLYG KRGGGKSLTS IALATKICKH
1260 1270 1280 1290 1300
YGVEPEKNIY TKPVASDYWD GYSGQLVCII DDIGQNTTDE DWSDFCQLVS
1310 1320 1330 1340 1350
GCPMRLNMAS LEEKGRHFSS PFIIATSNWS NPSPKTVYVK EAIDRRLHFK
1360 1370 1380 1390 1400
IEVKPASFFQ NPHNDMLNVN LAKTSDAIKD MSCVDLIMDG HNISLMDLLS
1410 1420 1430 1440 1450
SLVMTVEIRK QNMTEFMELW SQGISDDDSA VAEFFQSFPS GEPSSSKLSG
1460 1470 1480 1490 1500
FFQSVTNHKW VAVGAAVGIL GVLVGGWFVY KHFSRKEEEP IPTEGVYHGV
1510 1520 1530 1540 1550
TKPKQVIKLD ADPVESQSTL EIAGLVRKNL VQFGVGEKNG CVRWVMNALG
1560 1570 1580 1590 1600
VKDDWLLVPS HAYKFEKDYE MMEFYFNRGG TYYSISAGNV VIQSLDVGFQ
1610 1620 1630 1640 1650
DVVLMKVPTI PKFRDITEHF IKKGDVPRAL NRLATLVTTV NGTPMLISEG
1660 1670 1680 1690 1700
PLKMEEKATY VHKKNDGTTV DLTVDQAWRG KGEGLPGMCG GALISSNQSI
1710 1720 1730 1740 1750
QNAILGIHVA GGNSILVAKL VTQEMFQNID KKIESQRIMK VEFSQCSMNV
1760 1770 1780 1790 1800
VSKTLFKKSP IHHHIDKDMI NFPAAMPFSR AEIDPMAVML SKYSLPMVEE
1810 1820 1830 1840 1850
PEGYKDVSIF FQNKIMGKSI LVDDFLDLDM AITGTPGIDA INMDSSPGFP
1860 1870 1880 1890 1900
YVQEKLTKRD LIWLHENGLL LGIHPRLAQR ILFNTVMMEN CSDLDVVFTT
1910 1920 1930 1940 1950
CPKDELRPLD KVLESKTRAI DACPLDYTIL CRMYWGPAIS YFHLNPGFHT
1960 1970 1980 1990 2000
GVAIGIDPDK QWDELFKTMI RFGDVGLDLD FSAFDASLSP FMIREAGRIM
2010 2020 2030 2040 2050
SEISGTPSHF GTALINTIIY SKHLLYNCCY HVYGSMPSGS PCTALLNSII
2060 2070 2080 2090 2100
NNINLYYVFA KIFRKSPVFF SQAVRILCYG DDVLVVFSRD IQIDNLDQIG
2110 2120 2130 2140 2150
QKIVHEFKEL GMTATSADKT VPQLKPVSEL TFLKRSFNLV EDRIRPAISE
2160 2170 2180 2190 2200
KTIWSLVAWQ RSNAEFEQNL ENAQWFAFMH GFEFYQKFYY FVQSCLEKEM
2210 2220
IEYRLKSYDW WRMRFYDQCF VCDLS
Length:2,225
Mass (Da):251,415
Last modified:November 23, 2004 - v1
Checksum:i2BDABEBDF163C22D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY644676 Genomic RNA. Translation: AAU87586.1.
L07693 Genomic RNA. No translation available.
PIRiPQ0432.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY644676 Genomic RNA. Translation: AAU87586.1.
L07693 Genomic RNA. No translation available.
PIRiPQ0432.

3D structure databases

ProteinModelPortaliQ5Y944.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

CDDicd00205. rhv_like. 2 hits.
Gene3Di2.60.120.20. 3 hits.
InterProiIPR004004. Helic/Pol/Pept_Calicivir-typ.
IPR000605. Helicase_SF3_ssDNA/RNA_vir.
IPR014759. Helicase_SF3_ssRNA_vir.
IPR024354. Hepatitis_A_VP1-2A.
IPR027417. P-loop_NTPase.
IPR000199. Peptidase_C3A/C3B_picornavir.
IPR009003. Peptidase_S1_PA.
IPR001676. Picornavirus_capsid.
IPR033703. Rhv-like.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR029053. Viral_coat.
[Graphical view]
PfamiPF12944. HAV_VP. 1 hit.
PF00548. Peptidase_C3. 1 hit.
PF00680. RdRP_1. 1 hit.
PF00073. Rhv. 2 hits.
PF00910. RNA_helicase. 1 hit.
[Graphical view]
PRINTSiPR00918. CALICVIRUSNS.
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS50507. RDRP_SSRNA_POS. 1 hit.
PS51218. SF3_HELICASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPOLG_HAVCF
AccessioniPrimary (citable) accession number: Q5Y944
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: November 23, 2004
Last modified: November 30, 2016
This is version 78 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

The need for an intact eIF4G factor for the initiation of translation of HAV results in an inability to shut off host protein synthesis by a mechanism similar to that of other picornaviruses.
CF53/Berne is a cell culture-adapted strain derived from CF-53 by serial passages in PLC/PRF/5 and FRhK-4 cells.

Caution

It is uncertain whether Met-1 or Met-3 is the initiator.Curated
Protein VP1 seems to have a heterogeneous C-terminus in cell culture. It may be reduced by a few amino acids compared to the sequence shown.Curated

Keywords - Technical termi

Complete proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.