Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P08617

- POLG_HAVHM

UniProt

P08617 - POLG_HAVHM

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 136 (01 Oct 2014)
      Sequence version 1 (01 Aug 1988)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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

    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 membrane Source: UniProtKB-SubCell
    2. host cell mitochondrial outer membrane Source: UniProtKB-SubCell
    3. integral to membrane of host cell Source: UniProtKB-KW
    4. membrane Source: UniProtKB-KW
    5. viral capsid Source: UniProtKB-KW

    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

    « Hide

    MNMSRQGIFQ TVGSGLDHIL SLADIEEEQM IQSVDRTAVT GASYFTSVDQ     50
    SSVHTAEVGS HQVEPLRTSV DKPGSKKTQG EKFFLIHSAD WLTTHALFHE 100
    VAKLDVVKLL YNEQFAVQGL LRYHTYARFG IEIQVQINPT PFQQGGLICA 150
    MVPGDQSYGS IASLTVYPHG LLNCNINNVV RIKVPFIYTR GAYHFKDPQY 200
    PVWELTIRVW SELNIGTGTS AYTSLNVLAR FTDLELHGLT PLSTQMMRNE 250
    FRVSTTENVV NLSNYEDARA KMSFALDQED WKSDPSQGGG IKITHFTTWT 300
    SIPTLAAQFP FNASDSVGQQ IKVIPVDPYF FQMTNTNPDQ KCITALASIC 350
    QMFCFWRGDL VFDFQVFPTK YHSGRLLFCF VPGNELIDVS GITLKQATTA 400
    PCAVMDITGV QSTLRFRVPW ISDTPYRVNR YTKSAHQKGE YTAIGKLIVY 450
    CYNRLTSPSN VASHVRVNVY LSAINLECFA PLYHAMDVTT QVGDDSGGFS 500
    TTVSTEQNVP DPQVGITTMK DLKGKANRGK MDVSGVQAPV GAITTIEDPV 550
    LAKKVPETFP ELKPGESRHT SDHMSIYKFM GRSHFLCTFT FNSNNKEYTF 600
    PITLSSTSNP PHGLPSTLRW FFNLFQLYRG PLDLTIIITG ATDVDGMAWF 650
    TPVGLAVDTP WVEKESALSI DYKTALGAVR FNTRRTGNIQ IRLPWYSYLY 700
    AVSGALDGLG DKTDSTFGLV SIQIANYNHS DEYLSFSCYL SVTEQSEFYF 750
    PRAPLNSNAM LSTESMMSRI AAGDLESSVD DPRSEEDKRF ESHIECRKPY 800
    KELRLEVGKQ RLKYAQEELS NEVLPPPRKM KGLFSQAKIS LFYTEEHEIM 850
    KFSWRGVTAD TRALRRFGFS LAAGRSVWTL EMDAGVLTGR LIRLNDEKWT 900
    EMKDDKIVSL IEKFTSNKYW SKVNFPHGML DLEEIAANSK DFPNMSETDL 950
    CFLLHWLNPK KINLADRMLG LSGVQEIKEQ GVGLIAECRT FLDSIAGTLK 1000
    SMMFGFHHSV TVEIINTVLC FVKSGILLYV IQQLNQDEHS HIIGLLRVMN 1050
    YADIGCSVIS CGKVFSKMLE TVFNWQMDSR MMELRTQSFS NWLRDICSGI 1100
    TIFKNFKDAI YWLYTKLKDF YEVNYGKKKD ILNILKDNQQ KIEKAIEEAD 1150
    EFCILQIQDV EKFEQYQKGV DLIQKLRTVH SMAQVDPNLM VHLSPLRDCI 1200
    ARVHQKLKNL GSINQAMVTR CEPVVCYLYG KRGGGKSLTS IALATKICKH 1250
    YGVEPEKNIY TKPVASDYWD GYSGQLVCII DDIGQNTTDE DWSDFCQLVS 1300
    GCPMRLNMAS LEEKGRHFSS PFIIATSNWS NPSPKTVYVK EAIDRRLHFK 1350
    VEVKPASFFK NPHNDMLNVN LAKTNDAIKD MSCVDLIMDG HNVSLMDLLS 1400
    SLVMTVEIRK QNMTEFMELW SQGISDDDND SAVAEFFQSF PSGEPSNSKL 1450
    SGFFQSVTNH KWVAVGAAVG ILGVLVGGWF VYKHFSRKEE EPIPAEGVYH 1500
    GVTKPKQVIK LDADPVESQS TLEIAGLVRK NLVQFGVGEK NGCVRWVMNA 1550
    LGVKDDWLLV PSHAYKFEKD YEMMEFYFNR GGTYYSISAG NVVIQSLDVG 1600
    FQDVVLMKVP TIPKFRDITQ HFIKKGDVPR ALNRLATLVT TVNGTPMLIS 1650
    EGPLKMEEKA TYVHKKNDGT TVDLTVDQAW RGKGEGLPGM CGGALVSSNQ 1700
    SIQNAILGIH VAGGNSILVA KLVTQEMFQN IDKKIESQRI MKVEFTQCSM 1750
    NVVSKTLFRK SPIYHHIDKT MINFPAAMPF SKAEIDPMAV MLSKYSLPIV 1800
    EEPEDYKEAS IFYQNKIVGK TQLVDDFLDL DMAITGAPGI DAINMDSSPG 1850
    FPYVQEKLTK RDLIWLDENG LLLGVHPRLA QRILFNTVMM ENCSDLDVVF 1900
    TTCPKDELRP LEKVLESKTR AIDACPLDYS ILCRMYWGPA ISYFHLNPGF 1950
    HTGVAIGIDP DRQWDELFKT MIRFGDVGLD LDFSAFDASL SPFMIREAGR 2000
    IMSELSGTPS HFGTALINTI IYSKHLLYNC CYHVCGSMPS GSPCTALLNS 2050
    IINNVNLYYV FSKIFGKSPV FFCQALKILC YGDDVLIVFS RDVQIDNLDL 2100
    IGQKIVDEFK KLGMTATSAD KNVPQLKPVS ELTFLKRSFN LVEDRIRPAI 2150
    SEKTIWSLIA WQRSNAEFEQ NLENAQWFAF MHGYEFYQKF YYFVQSCLEK 2200
    EMIEYRLKSY DWWRMRFYDQ CFICDLS 2227
    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 1, 2014
    This is version 136 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