P27401 · POL_SFV3L

Function

function

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-Lys1,2 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 at least the viral genome, matrix protein, and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from the 3' end of the viral DNA right (U5) end, leaving the left (U3) intact. In the second step, the PIC enters cell nucleus. This process is mediated through the integrase and allows the virus to infect both dividing (nuclear membrane disassembled) and G1/S-arrested cells (active translocation), but with no viral gene expression in the latter. In 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. It is however not clear how integration then proceeds to resolve the asymmetrical cleavage of viral DNA (By similarity).

Miscellaneous

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.
Foamy viruses are distinct from other retroviruses in many respects. Their protease is active as an uncleaved Pro-Pol protein. Mature particles do not include the usual processed retroviral structural protein (MA, CA and NC), but instead contain two large Gag proteins. Their functional nucleic acid appears to be either RNA or dsDNA (up to 20% of extracellular particles), because they probably proceed either to an early (before integration) or late reverse transcription (after assembly). Foamy viruses have the ability to retrotranspose intracellularly with high efficiency. They bud predominantly into the endoplasmic reticulum (ER) and occasionally at the plasma membrane. Budding requires the presence of Env proteins. Most viral particles probably remain within the infected cell.

Catalytic activity

Cofactor

Protein has several cofactor binding sites:
Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Note: Binds 2 magnesium ions for reverse transcriptase polymerase activity.
Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Note: Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding.
Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Note: Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions.

Features

Showing features for active site, binding site, site.

TypeIDPosition(s)Description
Active site24For protease activity
Binding site252Mg2+ 1 (UniProtKB | ChEBI); catalytic; for reverse transcriptase activity
Binding site314Mg2+ 1 (UniProtKB | ChEBI); catalytic; for reverse transcriptase activity
Binding site315Mg2+ 1 (UniProtKB | ChEBI); catalytic; for reverse transcriptase activity
Site596-597Cleavage; by viral protease; partial
Binding site599Mg2+ 2 (UniProtKB | ChEBI); catalytic; for RNase H activity
Binding site646Mg2+ 2 (UniProtKB | ChEBI); catalytic; for RNase H activity
Binding site669Mg2+ 2 (UniProtKB | ChEBI); catalytic; for RNase H activity
Binding site740Mg2+ 2 (UniProtKB | ChEBI); catalytic; for RNase H activity
Site751-752Cleavage; by viral protease
Binding site873Mg2+ 3 (UniProtKB | ChEBI); catalytic; for integrase activity
Binding site935Mg2+ 3 (UniProtKB | ChEBI); catalytic; for integrase activity

GO annotations

AspectTerm
Cellular Componenthost cell
Cellular Componenthost cell cytoplasm
Cellular Componenthost cell nucleus
Cellular Componentvirion component
Molecular Functionaspartic-type endopeptidase activity
Molecular FunctionDNA-directed DNA polymerase activity
Molecular Functionmetal ion binding
Molecular FunctionRNA binding
Molecular FunctionRNA-directed DNA polymerase activity
Molecular FunctionRNA-DNA hybrid ribonuclease activity
Biological ProcessDNA integration
Biological ProcessDNA recombination
Biological Processestablishment of integrated proviral latency
Biological Processproteolysis
Biological Processsymbiont entry into host cell
Biological Processviral genome integration into host DNA
Biological Processviral penetration into host nucleus

Keywords

Protein family/group databases

Names & Taxonomy

Protein names

Gene names

    • Name
      pol

Organism names

Accessions

  • Primary accession
    P27401

Proteomes

Subcellular Location

Integrase

Virion
Host nucleus
Note: Nuclear at initial phase, cytoplasmic at assembly.

Protease/Reverse transcriptase/ribonuclease H

Host nucleus
Note: Nuclear at initial phase, cytoplasmic at assembly.

Keywords

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00002454521-596Protease/Reverse transcriptase
ChainPRO_00002454511-751Protease/Reverse transcriptase/ribonuclease H
ChainPRO_00001254851-1143Pro-Pol polyprotein
ChainPRO_0000245453597-751Ribonuclease H
ChainPRO_0000245454752-1143Integrase

Post-translational modification

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.

Interaction

Subunit

The protease is a homodimer, whose active site consists of two apposed aspartic acid residues.

Structure

3D structure databases

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain1-143Peptidase A9
Domain186-363Reverse transcriptase
Domain590-748RNase H type-1
Domain864-1023Integrase catalytic

Domain

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-x35-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).

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,143
  • Mass (Da)
    129,615
  • Last updated
    2006-07-11 v2
  • Checksum
    5E5350D0790CF2F3
MDPLQLLQPLEAEIKGTKLKAHWDSGATITCVPQAFLEEEVPIKNIWIKTIHGEKEQPVYYLTFKIQGRKVEAEVISSPYDYILVSPSDIPWLMKKPLQLTTLVPLQEYEERLLKQTMLTGSYKEKLQSLFLKYDALWQHWENQVGHRRIKPHHIATGTVNPRPQKQYPINPKAKASIQTVINDLLKQGVLIQQNSIMNTPVYPVPKPDGKWRMVLDYREVNKTIPLIAAQNQHSAGILSSIFRGKYKTTLDLSNGFWAHSITPESYWLTAFTWLGQQYCWTRLPQGFLNSPALFTADVVDLLKEVPNVQVYVDDIYISHDDPREHLEQLEKVFSLLLNAGYVVSLKKSEIAQHEVEFLGFNITKEGRGLTETFKQKLLNITPPRDLKQLQSILGLLNFARNFIPNFSELVKPLYNIIATANGKYITWTTDNSQQLQNIISMLNSAENLEERNPEVRLIMKVNTSPSAGYIRFYNEFAKRPIMYLNYVYTKAEVKFTNTEKLLTTIHKGLIKALDLGMGQEILVYSPIVSMTKIQKTPLPERKALPIRWITWMSYLEDPRIQFHYDKTLPELQQVPTVTDDIIAKIKHPSEFSMVFYTDGSAIKHPNVNKSHNAGMGIAQVQFKPEFTVINTWSIPLGDHTAQLAEVAAVEFACKKALKIDGPVLIVTDSFYVAESVNKELPYWQSNGFFNNKKKPLKHVSKWKSIADCIQLKPDIIIIHEKGHQPTASTFHTEGNNLADKLATQGSYVVNINTTPSLDAELDQLLQGQYPKGFPKHYQYQLENGQVMVTRPNGKRIIPPKSDRPQIILQAHNIAHTGRDSTFLKVSSKYWWPNLRKDVVKVIRQCKQCLVTNAATLAAPPILRPERPVKPFDKFFIDYIGPLPPSNGYLHVLVVVDSMTGFVWLYPTKAPSTSATVKALNMLTSIAVPKVIHSDQGAAFTSATFADWAKNKGIQLEFSTPYHPQSSGKVERKNSDIKRLLTKLLVGRPAKWYDLLPVVQLALNNSYSPSSKYTPHQLLFGIDSNTPFANSDTLDLSREEELSLLQEIRSSLYLPSTPPASIRAWSPSVGQLVQERVARPASLRPRWHKPTPVLEVINPRAVVILDHLGNRRTVSVDNLKLTAYQKDGTPNESAAVVAMEKDE

Sequence caution

The sequence AAA47796.1 differs from that shown. Reason: Erroneous initiation

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M74895
EMBL· GenBank· DDBJ
AAA47796.1
EMBL· GenBank· DDBJ
Genomic DNA Different initiation

Genome annotation databases

Similar Proteins

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