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P08617

- POLG_HAVHM

UniProt

P08617 - POLG_HAVHM

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Protein

Genome polyprotein

Gene
N/A
Organism
Human hepatitis A virus genotype IB (isolate HM175) (HHAV) (Human hepatitis A virus (isolate Human/Australia/HM175/1976))
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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.
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 pentamerization of P1-2A, which is the precursor of the structural proteins. 2A is proteolytically removed from particulate VP1-2A by a host protease and does not seem to be found in mature particles.
Protein 2B and 2BC precursor affect membrane integrity and cause an increase in membrane permeability.
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.
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.
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.
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.
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.
RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals.

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)LengthDescriptionGraphical viewFeature identifierActions
Sitei23 – 242CleavageSequence Analysis
Sitei245 – 2462Cleavage; by protease 3CSequence Analysis
Sitei491 – 4922Cleavage; by protease 3CSequence Analysis
Sitei769 – 7702Cleavage; by hostSequence Analysis
Sitei769 – 7691Important for VP1 folding and capsid assembly
Sitei836 – 8372Cleavage; by protease 3C
Sitei1087 – 10882Cleavage; by protease 3CSequence Analysis
Sitei1422 – 14232Cleavage; by protease 3CSequence Analysis
Sitei1496 – 14972Cleavage; by protease 3CSequence Analysis
Sitei1519 – 15202Cleavage; by protease 3CSequence Analysis
Active sitei1563 – 15631For protease 3C activity
Active sitei1603 – 16031For protease 3C activity
Active sitei1691 – 16911For protease 3C activity
Sitei1738 – 17392Cleavage; by protease 3C

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi1230 – 12378ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. cysteine-type endopeptidase activity Source: InterPro
  3. ion channel activity Source: UniProtKB-KW
  4. RNA binding Source: UniProtKB-KW
  5. RNA-directed RNA polymerase activity Source: UniProtKB-KW
  6. RNA helicase activity Source: InterPro
  7. structural molecule activity Source: InterPro

GO - Biological processi

  1. pore formation by virus in membrane of host cell Source: UniProtKB-KW
  2. protein oligomerization Source: UniProtKB-KW
  3. RNA-protein covalent cross-linking Source: UniProtKB-KW
  4. suppression by virus of host gene expression Source: UniProtKB-KW
  5. suppression by virus of host MAVS activity Source: UniProtKB-KW
  6. suppression by virus of host MAVS activity by MAVS proteolysis Source: UniProtKB
  7. transcription, DNA-templated Source: InterPro
  8. viral entry into host cell Source: UniProtKB-KW
  9. viral RNA genome replication Source: InterPro
  10. virion attachment to host cell Source: UniProtKB-KW
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 IB (isolate HM175) (HHAV) (Human hepatitis A virus (isolate Human/Australia/HM175/1976))
Taxonomic identifieri12098 [NCBI]
Taxonomic lineageiVirusesssRNA positive-strand viruses, no DNA stagePicornaviralesPicornaviridaeHepatovirus
Virus hostiCercopithecus hamlyni (Owl-faced monkey) (Hamlyn's monkey) [TaxID: 9536]
Homo sapiens (Human) [TaxID: 9606]
Macaca (macaques) [TaxID: 9539]
Pan troglodytes (Chimpanzee) [TaxID: 9598]
ProteomesiUP000006724: Genome

Subcellular locationi

Chain Protein 2B : 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.
Chain 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.
Chain Protein 3ABC : Host cytoplasmic vesicle membrane Curated; Peripheral membrane protein Curated; Cytoplasmic side Curated. Host mitochondrion outer 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.
Chain Protein 3AB : 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.
Chain Protein 3A : 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.
Chain 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.

GO - Cellular componenti

  1. host cell cytoplasmic vesicle Source: UniProtKB-KW
  2. host cell mitochondrial outer membrane Source: UniProtKB-KW
  3. integral to membrane of host cell Source: UniProtKB-KW
  4. membrane Source: UniProtKB-KW
  5. viral capsid Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi769 – 7691R → M: Complete loss of viral particles assembly. 1 Publication
Mutagenesisi836 – 8361Q → N: Partial loss of 2A-2B cleavage. 1 Publication
Mutagenesisi836 – 8361Q → R: Complete loss of 2A-2B cleavage. 1 Publication
Mutagenesisi1671 – 16711T → A: Complete loss of enzymatic activity.
Mutagenesisi1691 – 16911C → A: Complete loss of proteolytic activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 22272227Genome polyproteinPRO_0000308969Add
BLAST
Chaini1 – 245245Protein VP0Sequence AnalysisPRO_0000308970Add
BLAST
Chaini1 – 2323Protein VP4Sequence AnalysisPRO_0000039946Add
BLAST
Chaini24 – 245222Protein VP2Sequence AnalysisPRO_0000039947Add
BLAST
Chaini246 – 491246Protein VP3Sequence AnalysisPRO_0000039948Add
BLAST
Chaini492 – 836345Protein VP1-2ASequence AnalysisPRO_0000308971Add
BLAST
Chaini492 – 769278Protein VP1Sequence AnalysisPRO_0000039949Add
BLAST
Chaini770 – 83667Protein 2ASequence AnalysisPRO_0000039950Add
BLAST
Chaini837 – 1422586Protein 2BCSequence AnalysisPRO_0000308972Add
BLAST
Chaini837 – 1087251Protein 2BSequence AnalysisPRO_0000039951Add
BLAST
Chaini1088 – 1422335Protein 2CSequence AnalysisPRO_0000039952Add
BLAST
Chaini1423 – 2227805Protein 3ABCDSequence AnalysisPRO_0000308973Add
BLAST
Chaini1423 – 1738316Protein 3ABCSequence AnalysisPRO_0000308974Add
BLAST
Chaini1423 – 151997Protein 3ABSequence AnalysisPRO_0000308975Add
BLAST
Chaini1423 – 149674Protein 3ASequence AnalysisPRO_0000039953Add
BLAST
Chaini1497 – 151923Protein 3BSequence AnalysisPRO_0000039954Add
BLAST
Chaini1520 – 2227708Protein 3CDSequence AnalysisPRO_0000308976Add
BLAST
Chaini1520 – 1738219Protease 3CSequence AnalysisPRO_0000039955Add
BLAST
Chaini1739 – 2227489RNA-directed RNA polymerase 3D-POLSequence AnalysisPRO_0000039956Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1499 – 14991O-(5'-phospho-RNA)-tyrosineBy similarity

Post-translational modificationi

Specific enzymatic cleavages by 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.9 Publications
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

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.6 Publications

Structurei

Secondary structure

1
2227
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi1521 – 153111
Beta strandi1532 – 15398
Beta strandi1545 – 155511
Beta strandi1557 – 15615
Helixi1562 – 15643
Turni1565 – 15673
Helixi1571 – 15733
Beta strandi1574 – 15807
Beta strandi1583 – 15886
Helixi1589 – 15913
Beta strandi1592 – 15954
Beta strandi1597 – 16004
Beta strandi1603 – 16086
Helixi1619 – 16213
Helixi1625 – 16306
Turni1631 – 16333
Beta strandi1636 – 16427
Beta strandi1645 – 16517
Beta strandi1655 – 166511
Beta strandi1667 – 16693
Beta strandi1671 – 168313
Beta strandi1694 – 16985
Helixi1700 – 17023
Beta strandi1706 – 17149
Beta strandi1717 – 17226
Helixi1725 – 17306

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HAVX-ray2.00A/B1520-1736[»]
1QA7X-ray1.90A/B/C/D1520-1736[»]
2H6MX-ray1.40A1520-1731[»]
2H9HX-ray1.39A1520-1731[»]
2HALX-ray1.35A1520-1731[»]
ProteinModelPortaliP08617.
SMRiP08617. Positions 1520-1735.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08617.

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 14671467CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini1483 – 2227745CytoplasmicSequence AnalysisAdd
BLAST

Intramembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Intramembranei1468 – 148215Sequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1204 – 1366163SF3 helicasePROSITE-ProRule annotationAdd
BLAST
Domaini1520 – 1716197Peptidase C3Add
BLAST
Domaini1976 – 2097122RdRp catalyticPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili1127 – 115226Sequence AnalysisAdd
BLAST

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

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.
IPR000199. Peptidase_C3A/C3B_picornavir.
IPR001676. Picornavirus_capsid.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR009003. Trypsin-like_Pept_dom.
IPR029053. Viral_coat.
[Graphical view]
PfamiPF12944. DUF3840. 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.
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.

P08617-1 [UniParc]FASTAAdd to Basket

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        10         20         30         40         50
MNMSRQGIFQ TVGSGLDHIL SLADIEEEQM IQSVDRTAVT GASYFTSVDQ
60 70 80 90 100
SSVHTAEVGS HQVEPLRTSV 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 FQMTNTNPDQ KCITALASIC
360 370 380 390 400
QMFCFWRGDL VFDFQVFPTK YHSGRLLFCF VPGNELIDVS GITLKQATTA
410 420 430 440 450
PCAVMDITGV QSTLRFRVPW ISDTPYRVNR YTKSAHQKGE YTAIGKLIVY
460 470 480 490 500
CYNRLTSPSN VASHVRVNVY LSAINLECFA PLYHAMDVTT QVGDDSGGFS
510 520 530 540 550
TTVSTEQNVP DPQVGITTMK 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 LSTESMMSRI AAGDLESSVD DPRSEEDKRF ESHIECRKPY
810 820 830 840 850
KELRLEVGKQ RLKYAQEELS NEVLPPPRKM KGLFSQAKIS LFYTEEHEIM
860 870 880 890 900
KFSWRGVTAD TRALRRFGFS LAAGRSVWTL EMDAGVLTGR LIRLNDEKWT
910 920 930 940 950
EMKDDKIVSL IEKFTSNKYW SKVNFPHGML DLEEIAANSK DFPNMSETDL
960 970 980 990 1000
CFLLHWLNPK KINLADRMLG LSGVQEIKEQ GVGLIAECRT FLDSIAGTLK
1010 1020 1030 1040 1050
SMMFGFHHSV TVEIINTVLC FVKSGILLYV IQQLNQDEHS HIIGLLRVMN
1060 1070 1080 1090 1100
YADIGCSVIS CGKVFSKMLE TVFNWQMDSR MMELRTQSFS NWLRDICSGI
1110 1120 1130 1140 1150
TIFKNFKDAI YWLYTKLKDF YEVNYGKKKD ILNILKDNQQ KIEKAIEEAD
1160 1170 1180 1190 1200
EFCILQIQDV EKFEQYQKGV DLIQKLRTVH SMAQVDPNLM VHLSPLRDCI
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
VEVKPASFFK NPHNDMLNVN LAKTNDAIKD MSCVDLIMDG HNVSLMDLLS
1410 1420 1430 1440 1450
SLVMTVEIRK QNMTEFMELW SQGISDDDND SAVAEFFQSF PSGEPSNSKL
1460 1470 1480 1490 1500
SGFFQSVTNH KWVAVGAAVG ILGVLVGGWF VYKHFSRKEE EPIPAEGVYH
1510 1520 1530 1540 1550
GVTKPKQVIK LDADPVESQS TLEIAGLVRK NLVQFGVGEK NGCVRWVMNA
1560 1570 1580 1590 1600
LGVKDDWLLV PSHAYKFEKD YEMMEFYFNR GGTYYSISAG NVVIQSLDVG
1610 1620 1630 1640 1650
FQDVVLMKVP TIPKFRDITQ HFIKKGDVPR ALNRLATLVT TVNGTPMLIS
1660 1670 1680 1690 1700
EGPLKMEEKA TYVHKKNDGT TVDLTVDQAW RGKGEGLPGM CGGALVSSNQ
1710 1720 1730 1740 1750
SIQNAILGIH VAGGNSILVA KLVTQEMFQN IDKKIESQRI MKVEFTQCSM
1760 1770 1780 1790 1800
NVVSKTLFRK SPIYHHIDKT MINFPAAMPF SKAEIDPMAV MLSKYSLPIV
1810 1820 1830 1840 1850
EEPEDYKEAS IFYQNKIVGK TQLVDDFLDL DMAITGAPGI DAINMDSSPG
1860 1870 1880 1890 1900
FPYVQEKLTK RDLIWLDENG LLLGVHPRLA QRILFNTVMM ENCSDLDVVF
1910 1920 1930 1940 1950
TTCPKDELRP LEKVLESKTR AIDACPLDYS ILCRMYWGPA ISYFHLNPGF
1960 1970 1980 1990 2000
HTGVAIGIDP DRQWDELFKT MIRFGDVGLD LDFSAFDASL SPFMIREAGR
2010 2020 2030 2040 2050
IMSELSGTPS HFGTALINTI IYSKHLLYNC CYHVCGSMPS GSPCTALLNS
2060 2070 2080 2090 2100
IINNVNLYYV FSKIFGKSPV FFCQALKILC YGDDVLIVFS RDVQIDNLDL
2110 2120 2130 2140 2150
IGQKIVDEFK KLGMTATSAD KNVPQLKPVS ELTFLKRSFN LVEDRIRPAI
2160 2170 2180 2190 2200
SEKTIWSLIA WQRSNAEFEQ NLENAQWFAF MHGYEFYQKF YYFVQSCLEK
2210 2220
EMIEYRLKSY DWWRMRFYDQ CFICDLS
Length:2,227
Mass (Da):251,508
Last modified:August 1, 1988 - v1
Checksum:i01E225E7AEB740A6
GO

Sequence cautioni

The sequence AAA45466.1 differs from that shown. Reason: Erroneous initiation.

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1825 – 18251D → V in AAA45476. (PubMed:2984684)Curated
Sequence conflicti1850 – 18501G → R in AAA45476. (PubMed:2984684)Curated
Sequence conflicti1856 – 18561E → G in AAA45476. (PubMed:2984684)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti77 – 771K → R in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.
Natural varianti315 – 3151D → A in strain: HM175/24a and HM175/43c.
Natural varianti336 – 3361T → K in strain: HM175/18f.
Natural varianti638 – 6381I → V in strain: HM175/24a.
Natural varianti688 – 6881N → S in strain: HM175/24a and HM175/43c.
Natural varianti762 – 7621S → P in strain: HM175/18f.
Natural varianti764 – 7641E → V in strain: HM175/7.
Natural varianti767 – 7671M → V in strain: HM175/24a and HM175/43c.
Natural varianti821 – 8211N → S in strain: HM175/7.
Natural varianti838 – 8381K → N in strain: HM175/18f, HM175/24a and HM175/43c.
Natural varianti849 – 8491I → M in strain: HM175/18f, HM175/24a and HM175/43c.
Natural varianti941 – 9411D → E in 24.
Natural varianti993 – 9931D → H in strain: HM175/18f, HM175/24a and HM175/43c.
Natural varianti1052 – 10521A → V in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.
Natural varianti1062 – 10621G → A in strain: HM175/7.
Natural varianti1109 – 11113AIY → GIC in strain: HM175/18f, HM175/24a and HM175/43c.
Natural varianti1118 – 11181K → M in strain: HM175/7.
Natural varianti1151 – 11511E → K in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.
Natural varianti1163 – 11631F → S in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.
Natural varianti1180 – 11801H → Y in strain: HM175/18f, HM175/24a and HM175/43c.
Natural varianti1212 – 12121S → F in strain: HM175/18f, HM175/24a and HM175/43c.
Natural varianti1229 – 12291Y → H in strain: HM175/18f, HM175/24a and HM175/43c.
Natural varianti1277 – 12771V → I in strain: HM175/7.
Natural varianti1407 – 14071E → D in strain: HM175/18f, HM175/24a and HM175/43c.
Natural varianti1428 – 14281Missing in strain: HM175/18f, HM175/24a and HM175/43c.
Natural varianti1480 – 14801F → V in strain: HM175/18f, HM175/24a and HM175/43c.
Natural varianti1487 – 14871R → H in strain: HM175/18f, HM175/24a and HM175/43c.
Natural varianti1500 – 15001H → Y in strain: HM175/7.
Natural varianti1507 – 15071Q → H in strain: HM175/18f, HM175/24a and HM175/43c.
Natural varianti1524 – 15241I → V in strain: HM175/43c.
Natural varianti1620 – 16201Q → E in strain: HM175/18f and HM175/24a.
Natural varianti1675 – 16751T → A in strain: HM175/43c.
Natural varianti1805 – 18051D → G in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.
Natural varianti1930 – 19301S → T in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.
Natural varianti1962 – 19621R → K in strain: HM175/18f, HM175/24a and HM175/43c.

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M14707 Genomic RNA. Translation: AAA45465.1.
M14707 Genomic RNA. Translation: AAA45466.1. Different initiation.
M16632 Genomic RNA. Translation: AAA45471.1.
M59808 Genomic RNA. Translation: AAA45467.1.
M59809 Genomic RNA. Translation: AAA45469.1.
M59810 Genomic RNA. Translation: AAA45468.1.
M14114 Genomic RNA. Translation: AAA45475.1.
M14115 Genomic RNA. Translation: AAA45476.1.
K00386 Genomic RNA. No translation available.
PIRiA03905.
A25981. GNNYHM.
A94149. GNNYMK.
RefSeqiNP_041007.1. NC_001489.1.
NP_041008.1. NC_001489.1.

Genome annotation databases

GeneIDi1493918.
1493919.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M14707 Genomic RNA. Translation: AAA45465.1 .
M14707 Genomic RNA. Translation: AAA45466.1 . Different initiation.
M16632 Genomic RNA. Translation: AAA45471.1 .
M59808 Genomic RNA. Translation: AAA45467.1 .
M59809 Genomic RNA. Translation: AAA45469.1 .
M59810 Genomic RNA. Translation: AAA45468.1 .
M14114 Genomic RNA. Translation: AAA45475.1 .
M14115 Genomic RNA. Translation: AAA45476.1 .
K00386 Genomic RNA. No translation available.
PIRi A03905.
A25981. GNNYHM.
A94149. GNNYMK.
RefSeqi NP_041007.1. NC_001489.1.
NP_041008.1. NC_001489.1.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1HAV X-ray 2.00 A/B 1520-1736 [» ]
1QA7 X-ray 1.90 A/B/C/D 1520-1736 [» ]
2H6M X-ray 1.40 A 1520-1731 [» ]
2H9H X-ray 1.39 A 1520-1731 [» ]
2HAL X-ray 1.35 A 1520-1731 [» ]
ProteinModelPortali P08617.
SMRi P08617. Positions 1520-1735.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 1493918.
1493919.

Miscellaneous databases

EvolutionaryTracei P08617.

Family and domain databases

Gene3Di 2.60.120.20. 3 hits.
InterProi IPR004004. Helic/Pol/Pept_Calicivir-typ.
IPR000605. Helicase_SF3_ssDNA/RNA_vir.
IPR014759. Helicase_SF3_ssRNA_vir.
IPR024354. Hepatitis_A_VP1-2A.
IPR000199. Peptidase_C3A/C3B_picornavir.
IPR001676. Picornavirus_capsid.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR009003. Trypsin-like_Pept_dom.
IPR029053. Viral_coat.
[Graphical view ]
Pfami PF12944. DUF3840. 1 hit.
PF00548. Peptidase_C3. 1 hit.
PF00680. RdRP_1. 1 hit.
PF00073. Rhv. 2 hits.
PF00910. RNA_helicase. 1 hit.
[Graphical view ]
PRINTSi PR00918. CALICVIRUSNS.
SUPFAMi SSF50494. SSF50494. 1 hit.
PROSITEi PS50507. RDRP_SSRNA_POS. 1 hit.
PS51218. SF3_HELICASE_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Complete nucleotide sequence of wild-type hepatitis A virus: comparison with different strains of hepatitis A virus and other picornaviruses."
    Cohen J.I., Ticehurst J.R., Purcell R.H., Buckler-White A., Baroudy B.M.
    J. Virol. 61:50-59(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    Strain: HM175/wt.
  2. "Complete nucleotide sequence of an attenuated hepatitis A virus: comparison with wild-type virus."
    Cohen J.I., Rosenblum B., Ticehurst J.R., Daemer R.J., Feinstone S.M., Purcell R.H.
    Proc. Natl. Acad. Sci. U.S.A. 84:2497-2501(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    Strain: HM175/7 MK-5.
  3. "Antigenic and genetic variation in cytopathic hepatitis A virus variants arising during persistent infection: evidence for genetic recombination."
    Lemon S.M., Murphy P.C., Shields P.A., Ping L.H., Feinstone S.M., Cromeans T., Jansen R.W.
    J. Virol. 65:2056-2065(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    Strain: HM175/18f, HM175/24a and HM175/43c.
  4. "Sequence analysis of hepatitis A virus cDNA coding for capsid proteins and RNA polymerase."
    Baroudy B.M., Ticehurst J.R., Miele T.A., Maizel J.V. Jr., Purcell R.H., Feinstone S.M.
    Proc. Natl. Acad. Sci. U.S.A. 82:2143-2147(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-854 AND 1724-2227.
  5. "Identification and site-directed mutagenesis of the primary (2A/2B) cleavage site of the hepatitis A virus polyprotein: functional impact on the infectivity of HAV RNA transcripts."
    Martin A., Escriou N., Chao S.-F., Girard M., Lemon S.M., Wychowski C.
    Virology 213:213-222(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 837-856, PROTEOLYTIC PROCESSING OF POLYPROTEIN, MUTAGENESIS OF GLN-836.
    Strain: HM175p35.
  6. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 2090-2227.
  7. "Proteolytic activity of hepatitis A virus 3C protein."
    Jia X.-Y., Ehrenfeld E., Summers D.F.
    J. Virol. 65:2595-2600(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
  8. "Hepatitis A virus polyprotein synthesis initiates from two alternative AUG codons."
    Tesar M., Harmon S.A., Summers D.F., Ehrenfeld E.
    Virology 186:609-618(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION OF N-TERMINUS.
    Strain: HM175/7.
  9. "Analysis of a potential myristoylation site in hepatitis A virus capsid protein VP4."
    Tesar M., Jia X.-Y., Summers D.F., Ehrenfeld E.
    Virology 194:616-626(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF PROTEIN VP4.
    Strain: HM175/7.
  10. "Primary cleavage of the HAV capsid protein precursor in the middle of the proposed 2A coding region."
    Jia X.-Y., Summers D.F., Ehrenfeld E.
    Virology 193:515-519(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
  11. "Expression of hepatitis A virus precursor protein P3 in vivo and in vitro: polyprotein processing of the 3CD cleavage site."
    Tesar M., Pak I., Jia X.-Y., Richards O.C., Summers D.F., Ehrenfeld E.
    Virology 198:524-533(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
  12. "Proteinase 3C-mediated processing of VP1-2A of two hepatitis A virus strains: in vivo evidence for cleavage at amino acid position 273/274 of VP1."
    Probst C., Jecht M., Gauss-Mueller V.
    J. Virol. 71:3288-3292(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
  13. "Induction of intracellular membrane rearrangements by HAV proteins 2C and 2BC."
    Teterina N.L., Bienz K., Egger D., Gorbalenya A.E., Ehrenfeld E.
    Virology 237:66-77(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF PROTEIN 2C, FUNCTION OF PROTEIN 2BC.
    Strain: HM175/24a, HM175/wt and HM175p35.
  14. "Membrane association and RNA binding of recombinant hepatitis A virus protein 2C."
    Kusov Y.Y., Probst C., Jecht M., Jost P.D., Gauss-Mueller V.
    Arch. Virol. 143:931-944(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION OF PROTEIN 2C, RNA-BINDING.
  15. "Processing of proteinase precursors and their effect on hepatitis A virus particle formation."
    Probst C., Jecht M., Gauss-Mueller V.
    J. Virol. 72:8013-8020(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
  16. "The human homolog of HAVcr-1 codes for a hepatitis A virus cellular receptor."
    Feigelstock D., Thompson P., Mattoo P., Zhang Y., Kaplan G.G.
    J. Virol. 72:6621-6628(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF CAPSID WITH HUMAN HAVCR1.
  17. "Mapping of protein domains of hepatitis A virus 3AB essential for interaction with 3CD and viral RNA."
    Beneduce F., Ciervo A., Kusov Y.Y., Gauss-Mueller V., Morace G.
    Virology 264:410-421(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF PROTEIN 3AB, SUBUNIT, INTERACTION OF PROTEIN 3AB WITH PROTEIN 3CD.
    Strain: HM175/7.
  18. "Hepatitis A virus capsid protein VP1 has a heterogeneous C terminus."
    Graff J., Richards O.C., Swiderek K.M., Davis M.T., Rusnak F., Harmon S.A., Jia X.-Y., Summers D.F., Ehrenfeld E.
    J. Virol. 73:6015-6023(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
    Strain: HM175p35 and HM175pE.
  19. "Membrane permeability induced by hepatitis A virus proteins 2B and 2BC and proteolytic processing of HAV 2BC."
    Jecht M., Probst C., Gauss-Mueller V.
    Virology 252:218-227(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF PROTEIN 2B, FUNCTION OF PROTEIN 2BC.
  20. "Intrinsic signals for the assembly of hepatitis A virus particles. Role of structural proteins VP4 and 2A."
    Probst C., Jecht M., Gauss-Mueller V.
    J. Biol. Chem. 274:4527-4531(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF PROTEIN VP1-2A, FUNCTION OF PROTEIN VP4.
  21. "Analysis of deletion mutants indicates that the 2A polypeptide of hepatitis A virus participates in virion morphogenesis."
    Cohen L., Benichou D., Martin A.
    J. Virol. 76:7495-7505(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF PROTEIN 2A.
    Strain: HM175/18f.
  22. "Homogenous hepatitis A virus particles. Proteolytic release of the assembly signal 2A from procapsids by factor Xa."
    Rachow A., Gauss-Mueller V., Probst C.
    J. Biol. Chem. 278:29744-29751(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE OF PROTEIN VP1-2A, SUBUNIT, MUTAGENESIS OF ARG-769.
  23. "Hepatitis A virus proteinase 3C binding to viral RNA: correlation with substrate binding and enzyme dimerization."
    Peters H., Kusov Y.Y., Meyer S., Benie A.J., Baeuml E., Wolff M., Rademacher C., Peters T., Gauss-Mueller V.
    Biochem. J. 385:363-370(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF CYS-1691.
  24. "Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor."
    Yang Y., Liang Y., Qu L., Chen Z., Yi M., Li K., Lemon S.M.
    Proc. Natl. Acad. Sci. U.S.A. 104:7253-7258(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF PROTEIN 3ABC, SUBCELLULAR LOCATION OF PROTEIN 3ABC, INTERACTION OF PROTEIN 3ABC WITH HUMAN MAVS.
    Strain: HM175/18f.
  25. "RNA interaction and cleavage of poly(C)-binding protein 2 by hepatitis A virus protease."
    Zhang B., Seitz S., Kusov Y., Zell R., Gauss-Mueller V.
    Biochem. Biophys. Res. Commun. 364:725-730(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE OF HOST PCBP2 BY PROTEASE 3C.
  26. "Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases."
    Allaire M., Chernaia M.M., Malcolm B.A., James M.N.
    Nature 369:72-76(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1520-1736.
  27. "The refined crystal structure of the 3C gene product from hepatitis A virus: specific proteinase activity and RNA recognition."
    Bergmann E.M., Mosimann S.C., Chernaia M.M., Malcolm B.A., James M.N.G.
    J. Virol. 71:2436-2448(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1520-1736.
  28. "Crystal structure of an inhibitor complex of the 3C proteinase from hepatitis A virus (HAV) and implications for the polyprotein processing in HAV."
    Bergmann E.M., Cherney M.M., Mckendrick J., Frormann S., Luo C., Malcolm B.A., Vederas J.C., James M.N.G.
    Virology 265:153-163(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1520-1736 IN COMPLEX WITH THE INHIBITOR IODOACETYL-VALYL-PHENYLALANYL-AMIDE.
  29. "An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors."
    Yin J., Cherney M.M., Bergmann E.M., Zhang J., Huitema C., Pettersson H., Eltis L.D., Vederas J.C., James M.N.G.
    J. Mol. Biol. 361:673-686(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1520-1731 IN COMPLEX WITH PEPTIDE-BASED KETONE INHIBITORS.

Entry informationi

Entry nameiPOLG_HAVHM
AccessioniPrimary (citable) accession number: P08617
Secondary accession number(s): P06443
, P26580, P26581, P26582, Q81082, Q81094
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: October 29, 2014
This is version 137 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.
Wild-type HM175 (HM175/wt) comes from a sample isolated from a patient in Australia in 1976 and subsequently passaged three times in marmosets. HM175/7 is an attenuated strain derived from HM175 by 32 passages in African green monkey kidney cells. HM175/18f, HM175/24a, and HM175/43c are cytopathic isolates derived from HM175 by serial passages in FRhK-4 cells.
Mutations in proteins 2B and 2C seem to be essential for strain HM175 adaptation to growth in cell culture.

Caution

It is uncertain whether Met-1 or Met-3 is the initiator. In vitro, both are used, with a preference for Met-3.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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3