P13901 (POLG_HAVMB) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 121. History...
Names and origin
|Sequence length||2227 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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.
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.
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.
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.
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.
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.
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.
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.
RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals By similarity.
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
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.
3AB precursor is a homodimer. 3AB precursor interacts with 3CD precursor. Protein 3ABC interacts with human MAVS By similarity.
Protein 2B: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. 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 By similarity.
Protein 2C: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. 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.
Protein 3ABC: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Host mitochondrion outer membrane; Peripheral membrane protein; Cytoplasmic side Potential. 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 By similarity.
Protein 3AB: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. 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 By similarity.
Protein 3A: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. 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 By similarity.
RNA-directed RNA polymerase 3D-POL: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. 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.
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.
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.
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.
Belongs to the picornaviridae polyprotein family.
Contains 1 peptidase C3 domain.
Contains 1 RdRp catalytic domain.
Contains 1 SF3 helicase domain.
It is uncertain whether Met-1 or Met-3 is the initiator.
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.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 2227||2227||Genome polyprotein||PRO_0000311015|
|Chain||1 – 245||245||Protein VP0 Potential||PRO_0000311016|
|Chain||1 – 23||23||Protein VP4 Potential||PRO_0000039968|
|Chain||24 – 245||222||Protein VP2 Potential||PRO_0000039969|
|Chain||246 – 491||246||Protein VP3 Potential||PRO_0000039970|
|Chain||492 – 836||345||Protein VP1-2A Potential||PRO_0000039971|
|Chain||492 – 769||278||Protein VP1 Potential||PRO_0000311017|
|Chain||770 – 836||67||Protein 2A Potential||PRO_0000039972|
|Chain||837 – 1422||586||Protein 2BC Potential||PRO_0000311018|
|Chain||837 – 1087||251||Protein 2B Potential||PRO_0000039973|
|Chain||1088 – 1422||335||Protein 2C Potential||PRO_0000039974|
|Chain||1423 – 2227||805||Protein 3ABCD Potential||PRO_0000311019|
|Chain||1423 – 1738||316||Protein 3ABC Potential||PRO_0000311020|
|Chain||1423 – 1519||97||Protein 3AB Potential||PRO_0000311021|
|Chain||1423 – 1496||74||Protein 3A Potential||PRO_0000039975|
|Chain||1497 – 1519||23||Protein 3B Potential||PRO_0000039976|
|Chain||1520 – 2227||708||Protein 3CD Potential||PRO_0000311022|
|Chain||1520 – 1738||219||Protease 3C Potential||PRO_0000039977|
|Chain||1739 – 2227||489||RNA-directed RNA polymerase 3D-POL||PRO_0000039978|
|Topological domain||1 – 1467||1467||Cytoplasmic Potential|
|Intramembrane||1468 – 1482||15||Potential|
|Topological domain||1483 – 2227||745||Cytoplasmic Potential|
|Domain||1204 – 1366||163||SF3 helicase|
|Domain||1520 – 1716||197||Peptidase C3|
|Domain||1976 – 2097||122||RdRp catalytic|
|Nucleotide binding||1230 – 1237||8||ATP Potential|
|Coiled coil||1127 – 1152||26||Potential|
|Compositional bias||636 – 639||4||Poly-Ile|
|Active site||1563||1||For protease 3C activity|
|Active site||1603||1||For protease 3C activity|
|Active site||1691||1||For protease 3C activity|
|Site||23 – 24||2||Cleavage Potential|
|Site||245 – 246||2||Cleavage; by protease 3C Potential|
|Site||491 – 492||2||Cleavage; by protease 3C Potential|
|Site||769 – 770||2||Cleavage; by host Potential|
|Site||769||1||Important for VP1 folding and capsid assembly By similarity|
|Site||836 – 837||2||Cleavage; by protease 3C By similarity|
|Site||1087 – 1088||2||Cleavage; by protease 3C Potential|
|Site||1422 – 1423||2||Cleavage; by protease 3C Potential|
|Site||1496 – 1497||2||Cleavage; by protease 3C Potential|
|Site||1519 – 1520||2||Cleavage; by protease 3C Potential|
|Site||1738 – 1739||2||Cleavage; by protease 3C By similarity|
Amino acid modifications
|Modified residue||1499||1||O-(5'-phospho-RNA)-tyrosine By similarity|
Helix Strand Turn
|Helix||1521 – 1531||11|
|Beta strand||1532 – 1538||7|
|Beta strand||1545 – 1555||11|
|Beta strand||1557 – 1561||5|
|Helix||1562 – 1564||3|
|Turn||1565 – 1567||3|
|Helix||1571 – 1573||3|
|Beta strand||1574 – 1580||7|
|Beta strand||1583 – 1588||6|
|Helix||1589 – 1591||3|
|Beta strand||1592 – 1600||9|
|Beta strand||1603 – 1608||6|
|Helix||1619 – 1621||3|
|Helix||1625 – 1631||7|
|Beta strand||1636 – 1642||7|
|Beta strand||1645 – 1651||7|
|Beta strand||1655 – 1665||11|
|Beta strand||1671 – 1683||13|
|Beta strand||1694 – 1698||5|
|Helix||1700 – 1702||3|
|Beta strand||1706 – 1714||9|
|Beta strand||1717 – 1722||6|
|Helix||1725 – 1730||6|
|||"The entire nucleotide sequence of the genome of human hepatitis A virus (isolate MBB)."|
Paul A.V., Tada H., der Helm K., Wissel T., Kiehn R., Wimmer E., Deinhardt F.
Virus Res. 8:153-171(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Dual modes of modification of hepatitis A virus 3C protease by a serine-derived beta-lactone: selective crystallization and formation of a functional catalytic triad in the active site."|
Yin J., Bergmann E.M., Cherney M.M., Lall M.S., Jain R.P., Vederas J.C., James M.N.G.
J. Mol. Biol. 354:854-871(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1520-1738 IN COMPLEX WITH THE INHIBITOR N-CBZ-L-SERINE B-LACTONE.
|M20273 Genomic RNA. Translation: AAA45474.1.|
3D structure databases
|SMR||P13901. Positions 1520-1735. |
Protocols and materials databases
Family and domain databases
|InterPro||IPR004004. Helic/Pol/Pept_Calicivir-typ. |
|Pfam||PF12944. DUF3840. 1 hit. |
PF00548. Peptidase_C3. 1 hit.
PF00680. RdRP_1. 1 hit.
PF00073. Rhv. 2 hits.
PF00910. RNA_helicase. 1 hit.
|PRINTS||PR00918. CALICVIRUSNS. |
|SUPFAM||SSF50494. SSF50494. 1 hit. |
|PROSITE||PS50507. RDRP_SSRNA_POS. 1 hit. |
PS51218. SF3_HELICASE_2. 1 hit.
|Accession||Primary (citable) accession number: P13901|
Secondary accession number(s): Q81083 Q81093
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|