| IED ID | IndEnz0002001476 |
| Enzyme Type ID | protease001476 |
| Protein Name |
Pro-Pol polyprotein Pr125Pol Cleaved into: Protease/Reverse transcriptase/ribonuclease H EC 2.7.7.49 EC 2.7.7.7 EC 3.1.26.4 EC 3.4.23.- p87Pro-RT-RNaseH ; Protease/Reverse transcriptase EC 2.7.7.49 EC 2.7.7.7 EC 3.4.23.- p65Pro-RT ; Ribonuclease H RNase H EC 3.1.26.4 ; Integrase IN EC 2.7.7.- EC 3.1.-.- p42In |
| Gene Name | pol |
| Organism | Feline foamy virus (FFV) (Feline syncytial virus) |
| Taxonomic Lineage | Viruses Riboviria Pararnavirae Artverviricota Revtraviricetes Ortervirales Retroviridae Spumaretrovirinae Felispumavirus Feline foamy virus (FFV) (Feline syncytial virus) |
| Enzyme Sequence | MDLLKPLTVERKGVKIKGYWDSQADITCVPKDLLQGEEPVRQQNVTTIHGTQEGDVYYVNLKIDGRRINTEVIGTTLDYAIITPGDVPWILKKPLELTIKLDLEEQQGTLLNNSILSKKGKEELKQLFEKYSALWQSWENQVGHRRIRPHKIATGTVKPTPQKQYHINPKAKPDIQIVINDLLKQGVLIQKESTMNTPVYPVPKPNGRWRMVLDYRAVNKVTPLIAVQNQHSYGILGSLFKGRYKTTIDLSNGFWAHPIVPEDYWITAFTWQGKQYCWTVLPQGFLNSPGLFTGDVVDLLQGIPNVEVYVDDVYISHDSEKEHLEYLDILFNRLKEAGYIISLKKSNIANSIVDFLGFQITNEGRGLTDTFKEKLENITAPTTLKQLQSILGLLNFARNFIPDFTELIAPLYALIPKSTKNYVPWQIEHSTTLETLITKLNGAEYLQGRKGDKTLIMKVNASYTTGYIRYYNEGEKKPISYVSIVFSKTELKFTELEKLLTTVHKGLLKALDLSMGQNIHVYSPIVSMQNIQKTPQTAKKALASRWLSWLSYLEDPRIRFFYDPQMPALKDLPAVDTGKDNKKHPSNFQHIFYTDGSAITSPTKEGHLNAGMGIVYFINKDGNLQKQQEWSISLGNHTAQFAEIAAFEFALKKCLPLGGNILVVTDSNYVAKAYNEELDVWASNGFVNNRKKPLKHISKWKSVADLKRLRPDVVVTHEPGHQKLDSSPHAYGNNLADQLATQASFKVHMTKNPKLDIEQIKAIQACQNNERLPVGYPKQYTYELQNNKCMVLRKDGWREIPPSRERYKLIKEAHNISHAGREAVLLKIQENYWWPKMKKDISSFLSTCNVCKMVNPLNLKPISPQAIVHPTKPFDKFYMDYIGPLPPSEGYVHVLVVVDAATGFTWLYPTKAQTSKATIKVLNHLTGLAIPKVLHSDQGSAFTSEEFAQWAKERNIQLEFSTPYHPQSSGKVERKNSEIKKLLTKLLVGRPLKWYNLISSVQLALNNTHVVSTKYTPHQLMFGIDCNLPFANKDTLDWTREEELALLQEIRESLQHPVQPPTCSGWSPYVGQLVQERVYRPSQLRPKWRKPTKVLEILNPRTVIIVDHLGQRKSVSIDNLKPTAHQHNGTRTCDDPEGMDGMECSQTTTETSVDSS |
| Enzyme Length | 1156 |
| Uniprot Accession Number | O93209 |
| Absorption | |
| Active Site | ACT_SITE 21; /note=For protease activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00863 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.4; Evidence={ECO:0000255|PROSITE-ProRule:PRU00408}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; |
| DNA Binding | |
| EC Number | 2.7.7.49; 2.7.7.7; 3.1.26.4; 3.4.23.-; 2.7.7.49; 2.7.7.7; 3.4.23.-; 3.1.26.4; 2.7.7.-; 3.1.-.- |
| Enzyme 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). {ECO:0000250}.; FUNCTION: 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). {ECO:0000250}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (5); Compositional bias (1); Domain (4); Metal binding (9); Region (1); Site (2) |
| Keywords | Aspartyl protease;DNA integration;DNA recombination;DNA-directed DNA polymerase;Endonuclease;Host cytoplasm;Host nucleus;Hydrolase;Magnesium;Metal-binding;Multifunctional enzyme;Nuclease;Nucleotidyltransferase;Protease;RNA-binding;RNA-directed DNA polymerase;Reference proteome;Transferase;Viral genome integration;Viral penetration into host nucleus;Virion;Virus entry into host cell |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Integrase]: Virion {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.; SUBCELLULAR LOCATION: [Protease/Reverse transcriptase/ribonuclease H]: Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}. |
| Modified Residue | |
| Post Translational Modification | PTM: 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). {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 131,499 |
| Kinetics | |
| Metal Binding | METAL 249; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000250; METAL 311; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000250; METAL 312; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000250; METAL 595; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000250; METAL 643; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000250; METAL 666; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000250; METAL 737; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000250; METAL 875; /note=Magnesium 3; catalytic; for integrase activity; /evidence=ECO:0000250; METAL 937; /note=Magnesium 3; catalytic; for integrase activity; /evidence=ECO:0000250 |
| Rhea ID | RHEA:22508 |
| Cross Reference Brenda |