| IED ID | IndEnz0002013053 |
| Enzyme Type ID | protease013053 |
| Protein Name |
Gag-Pol polyprotein Cleaved into: Matrix protein p16; Capsid protein p25; Nucleocapsid protein p14; Protease EC 3.4.23.- Retropepsin ; Reverse transcriptase/ribonuclease H RT EC 2.7.7.49 EC 2.7.7.7 EC 3.1.26.4 Exoribonuclease H EC 3.1.13.2 ; Deoxyuridine 5'-triphosphate nucleotidohydrolase dUTPase EC 3.6.1.23 ; Integrase IN EC 2.7.7.- EC 3.1.-.- |
| Gene Name | pol |
| Organism | Maedi visna virus (strain 1514 / clone LV1-1KS2) (MVV) (Visna lentivirus) |
| Taxonomic Lineage | Viruses Riboviria Pararnavirae Artverviricota Revtraviricetes Ortervirales Retroviridae Orthoretrovirinae Lentivirus Visna-maedi virus Visna/maedi virus 1514 Maedi visna virus (strain 1514 / clone LV1-1KS2) (MVV) (Visna lentivirus) |
| Enzyme Sequence | MAKQGSKEKKGYPELKEVIKATCKIRVGPGKETLTEGNCLWALKTIDFIFEDLKTEPWTITKMYTVWDRLKGLTPEETSKREFASLQATLACIMCSQMGMKPETVQAAKGIISMKEGLQENKEAKGEKVEQLYPNLEKHREVYPIVNLQAGGRSWKAVESVVFQQLQTVAMQHGLVSEDFERQLAYYATTWTSKDILEVLVMMPGNRAQKELIQGKLNEEAERWVRQNPPGPNVLTVDQIMGVGQTNQQASQANMDQARQICLQWVITALRSVRHMSHRPGNPMLVKQKNTESYEDFIARLLEAIDAEPVMDPIKTYLKVTLSYTNASTDCQKQMDRTLGTRVQQATVEEKMQACRDVGSEGFKMQLLAQALRPQGKAGHKGVNQKCYNCGKPGHLARQCRQGIICHHCGKRGHMQKDCRQKKQQGKQQEGATCGAVRAPYVVTEAPPKIEIKVGTRWKKLLVDTGADKTIVTSHDMSGIPKGRIILQGIGGIIEGEKWEQVHLQYKDKMIKGTIVVLATSPVEVLGRDNMRELGIGLIMANLEEKKIPSTRVRLKEGCKGPHIAQWPLTQEKLEGLKEIVDRLEKEGKVGRAPPHWTCNTPIFCIKKKSGKWRMLIDFRELNKQTEDLAEAQLGLPHPGGLQRKKHVTILDIGDAYFTIPLYEPYRQYTCFTMLSPNNLGPCVRYYWKVLPQGWKLSPAVYQFTMQKILRGWIEEHPMIQFGIYMDDIYIGSDLGLEEHRGIVNELASYIAQYGFMLPEDKRQEGYPAKWLGFELHPEKWKFQKHTLPEITEGPITLNKLQKLVGDLVWRQSLIGKSIPNILKLMEGDRALQSERYIESIHVREWEACRQKLKEMEGNYYDEEKDIYGQLDWGNKAIEYIVFQEKGKPLWVNVVHSIKNLSQAQQIIKAAQKLTQEVIIRTGKIPWILLPGREEDWILELQMGNINWMPSFWSCYKGSVRWKKRNVIAEVVPGPTYYTDGGKKNGRGSLGYIASTGEKFRIHEEGTNQQLELRAIEEACKQGPEKMNIVTDSRYAYEFMLRNWDEEVIRNPIQARIMELVHNKEKIGVHWVPGHKGIPQNEEIDRYISEIFLAKEGRGILQKRAEDAGYDLICPQEISIPAGQVKRIAIDLKINLKKDQWAMIGTKSSFANKGVFVQGGIIDSGYQGTIQVVIYNSNNKEVVIPQGRKFAQLILMPLIHEELKPWGETRKTERGEQGFGSTGMYWIENIPLAEEEHNKWHQDAVSLHLEFGIPRTAAEDIVQQCDVCQENKMPSTLRGSNKRGIDHWQVDYTHYEDKIILVWVETNSGLIYAERVKGETGQEFRVQTMKWYAMFAPKSLQSDNGPAFVAESTQLLMKYLGIEHTTGIPWNPQSQALVERTHQTLKNTLEKLIPMFNAFESALAGTLITLNIKRKGGLGTSPMDIFIFNKEQQRIQQQSKSKQEKIRFCYYRTRKRGHPGEWQGPTQVLWGGDGAIVVKDRGTDRYLVIANKDVKFIPPPKEIQKE |
| Enzyme Length | 1506 |
| Uniprot Accession Number | P23427 |
| Absorption | |
| Active Site | ACT_SITE 464; /note=Protease; shared with dimeric partner; /evidence=ECO:0000255|PROSITE-ProRule:PRU00275 |
| 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=3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.; EC=3.1.13.2; CATALYTIC ACTIVITY: Reaction=dUTP + H2O = diphosphate + dUMP + H(+); Xref=Rhea:RHEA:10248, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:61555, ChEBI:CHEBI:246422; EC=3.6.1.23; 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 | DNA_BIND 1447..1499; /note=Integrase-type; /evidence=ECO:0000255|PROSITE-ProRule:PRU00506 |
| EC Number | 3.4.23.-; 2.7.7.49; 2.7.7.7; 3.1.26.4; 3.1.13.2; 3.6.1.23; 2.7.7.-; 3.1.-.- |
| Enzyme Function | FUNCTION: [Gag-Pol polyprotein]: Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Matrix protein p16]: Targets the polyprotein to the plasma membrane. {ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Capsid protein p25]: Forms the core that encapsulates the genomic RNA-nucleocapsid complex in the virion. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Nucleocapsid protein p14]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearrangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Protease]: The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. {ECO:0000255|PROSITE-ProRule:PRU00275}.; FUNCTION: [Reverse transcriptase/ribonuclease H]: RT is a multifunctional enzyme that converts the viral dimeric RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays 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-Trp 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 perfom 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 perfom 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 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 primers. 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. {ECO:0000255|PROSITE-ProRule:PRU00405}.; FUNCTION: [Integrase]: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. {ECO:0000250|UniProtKB:P03370}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (8); DNA binding (1); Domain (4); Erroneous gene model prediction (1); Metal binding (14); Site (1); Zinc finger (3) |
| Keywords | Aspartyl protease;Capsid protein;DNA integration;DNA recombination;DNA-binding;Endonuclease;Hydrolase;Magnesium;Metal-binding;Multifunctional enzyme;Nuclease;Nucleotide metabolism;Nucleotidyltransferase;Protease;RNA-directed DNA polymerase;Repeat;Ribosomal frameshifting;Transferase;Viral genome integration;Virion;Virus entry into host cell;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Matrix protein p16]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein p25]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p14]: Virion {ECO:0000305}. |
| Modified Residue | |
| Post Translational Modification | PTM: [Gag-Pol polyprotein]: Specific enzymatic cleavages by the viral protease yield mature proteins. {ECO:0000305}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 171,974 |
| Kinetics | |
| Metal Binding | METAL 652; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00405; METAL 727; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00405; METAL 728; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00405; METAL 980; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1012; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1032; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1085; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1237; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00450; METAL 1241; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00450; METAL 1265; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00450; METAL 1268; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00450; METAL 1291; /note=Magnesium 3; catalytic; for integrase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00457; METAL 1343; /note=Magnesium 3; catalytic; for integrase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00457; METAL 1379; /note=Magnesium 3; catalytic; for integrase activity; /evidence=ECO:0000305 |
| Rhea ID | RHEA:10248; RHEA:22508 |
| Cross Reference Brenda |