Q9TTC1 (POL_KORV) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 74. History...
Names and origin
|Protein names||Recommended name:|
|Organism||Koala retrovirus (KoRV) [Complete proteome]|
|Taxonomic identifier||394239 [NCBI]|
|Taxonomic lineage||Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Gammaretrovirus › unclassified Gammaretrovirus|
|Virus host||Phascolarctos cinereus (Koala) [TaxID: 38626]|
|Sequence length||1127 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Inferred from homology|
General annotation (Comments)
The aspartyl protease activity mediates proteolytic cleavages of Gag and Pol polyproteins. The reverse transcriptase (RT) activity converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell (early reverse transcription) or after proviral DNA transcription (late reverse transcription). RT consists of a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for a polypurine tract (PPT) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPT that has not been removed by RNase H as primer. PPT and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends By similarity.
Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA. In the second step, the PIC access cell chromosomes during cell division. The third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5'-ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands (see above) are filled in and then ligated By similarity.
Endonucleolytic cleavage to 5'-phosphomonoester.
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Binds 2 magnesium ions for reverse transcriptase polymerase activity By similarity.
Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding By similarity.
Magnesium ions for integrase activity. Binds at least 1, maybe 2 magnesium ions By similarity.
The reverse transcriptase/ribonuclease H (RT) is structured in five subdomains: finger, palm, thumb, connection and RNase H. Within the palm subdomain, the "primer grip" region is thought to be involved in the positioning of the primer terminus for accommodating the incoming nucleotide. The RNase H domain stabilizes the association of RT with primer-template By similarity.
Integrase core domain contains the D-x(n)-D-x(35)-E motif, named for the phylogenetically conserved glutamic acid and aspartic acid residues and the invariant 35 amino acid spacing between the second and third acidic residues. Each acidic residue of the D,D35E motif is independently essential for the 3'-processing and strand transfer activities of purified integrase protein By similarity.
Specific enzymatic cleavages in vivo by viral protease yield mature proteins. The protease is not cleaved off from Pol. Since cleavage efficiency is not optimal for all sites, long and active p65Pro-RT, p87Pro-RT-RNaseH and even some Pr125Pol are detected in infected cells By similarity.
The reverse transcriptase is an error-prone enzyme that lacks a proof-reading function. High mutations rate is a direct consequence of this characteristic. RT also displays frequent template switching leading to high recombination rate. Recombination mostly occurs between homologous regions of the two copackaged RNA genomes. If these two RNA molecules derive from different viral strains, reverse transcription will give rise to highly recombinated proviral DNAs.
Koala retrovirus is both a circulating virus and an endogenous retrovirus of koala, except in some isolated populations in south Australia.
Contains 1 integrase catalytic domain.
Contains 1 peptidase A2 domain.
Contains 1 reverse transcriptase domain.
Contains 1 RNase H domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 1127||1127||Pro-Pol polyprotein||PRO_0000249431|
|Chain||1 – ?742||742||Protease/Reverse transcriptase/ribonuclease H By similarity||PRO_0000249432|
|Chain||?743 – 1127||385||Integrase By similarity||PRO_0000249433|
|Domain||22 – 92||71||Peptidase A2|
|Domain||202 – 393||192||Reverse transcriptase|
|Domain||635 – 781||147||RNase H|
|Domain||905 – 1063||159||Integrase catalytic|
|Metal binding||229||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||303||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||304||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||661||1||Magnesium; catalytic; for RNase H activity By similarity|
|Metal binding||731||1||Magnesium; catalytic; for RNase H activity By similarity|
|Metal binding||904||1||Magnesium; catalytic; for integrase activity By similarity|
|Site||?742 – ?743||2||Cleavage; by viral protease By similarity|
|||"The nucleotide sequence of koala (Phascolarctos cinereus) retrovirus: a novel type C endogenous virus related to Gibbon ape leukemia virus."|
Hanger J.J., Bromham L.D., McKee J.J., O'Brien T.M., Robinson W.F.
J. Virol. 74:4264-4272(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|AF151794 Genomic DNA. Translation: AAF15098.1.|
3D structure databases
|SMR||Q9TTC1. Positions 103-552, 583-738. |
Protein family/group databases
Protocols and materials databases
Family and domain databases
|InterPro||IPR001584. Integrase_cat-core. |
|Pfam||PF00075. RNase_H. 1 hit. |
PF00665. rve. 1 hit.
PF00077. RVP. 1 hit.
PF00078. RVT_1. 1 hit.
|SUPFAM||SSF50630. SSF50630. 1 hit. |
SSF53098. SSF53098. 2 hits.
|PROSITE||PS50175. ASP_PROT_RETROV. 1 hit. |
PS50994. INTEGRASE. 1 hit.
PS50879. RNASE_H. 1 hit.
PS50878. RT_POL. 1 hit.
|Accession||Primary (citable) accession number: Q9TTC1|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|