| IED ID | IndEnz0002013300 |
| Enzyme Type ID | protease013300 |
| Protein Name |
Gag-Pro-Pol polyprotein Cleaved into: Matrix protein p10; Phosphorylated protein pp21; Protein p3; Protein p8; Protein n; Capsid protein p27; Nucleocapsid protein-dUTPase NC-dUTPase EC 3.6.1.23 ; Protease EC 3.4.23.- ; Reverse transcriptase/ribonuclease H RT EC 2.7.7.49 EC 2.7.7.7 EC 3.1.26.4 ; Integrase IN EC 2.7.7.- EC 3.1.-.- |
| Gene Name | gag-pro-pol |
| Organism | Mouse mammary tumor virus (strain C3H) (MMTV) |
| Taxonomic Lineage | Viruses Riboviria Pararnavirae Artverviricota Revtraviricetes Ortervirales Retroviridae Orthoretrovirinae Betaretrovirus Mouse mammary tumor virus (MMTV) Mouse mammary tumor virus (strain C3H) (MMTV) |
| Enzyme Sequence | MGVSGSKGQKLFVSVLQRLLSERGLHVKESSAIEFYQFLIKVSPWFPEEGGLNLQDWKRVGREMKKYAAEHGTDSIPKQAYPIWLQLREILTEQSDLVLLSAEAKSVTEEELEEGLTGLLSASSQEKTYGTRGTAYAEIDTEVDKLSEHIYDEPYEEKEKADKNEEKDHVRKVKKIVQRKENSEHKRKEKDQKAFLATDWNNDDLSPEDWDDLEEQAAHYHDDDELILPVKRKVDKKKPLALRRKPLPPVGFAGAMAEAREKGDLTFTFPVVFMGESDDDDTPVWEPLPLKTLKELQSAVRTMGPSAPYTLQVVDMVASQWLTPSDWHQTARATLSPGDYVLWRTEYEEKSKETVQKTAGKRKGKVSLDMLLGTGQFLSPSSQIKLSKDVLKDVTTNAVLAWRAIPPPGVKKTVLAGLKQGNEESYETFISRLEEAVYRMMPRGEGSDILIKQLAWENANSLCQDLIRPMRKTGTMQDYIRACLDASPAVVQGMAYAAAMRGQKYSTFVKQTYGGGKGGQGSEGPVCFSCGKTGHIKRDCKEEKGSKRAPPGLCPRCKKGYHWKSECKSKFDKDGNPLPPLETNAENSKNLVKGQSPSPTQKGDKGKDSGLNPEAPPFTIHDLPRGTPGSAGLDLSSQKDLILSLEDGVSLVPTLVKGTLPEGTTGLIIGRSSNYKKGLEVLPGVIDSDFQGEIKVMVKAAKNAVIIHKGERIAQLLLLPYLKLPNPIIKEERGSEGFGSTSHVHWVQEISDSRPMLHISLNGRRFLGLLDTGADKTCIAGRDWPANWPIHQTESSLQGLGMACGVARSSQPLRWQHEDKSGIIHPFVIPTLPFTLWGRDIMKEIKVRLMTDSPDDSQDLMIGAIESNLFADQISWKSDQPVWLNQWPLKQEKLQALQQLVTEQLQLGHLEESNSPWNTPVFVIKKKSGKWRLLQDLRAVNATMHDMGALQPGLPSPVAVPKGWEIIIIDLQDCFFNIKLHPEDCKRFAFSVPSPNFKRPYQRFQWKVLPQGMKNSPTLCQKFVDKAILTVRDKYQDSYIVHYMDDILLAHPSRSIVDEILTSMIQALNKHGLVVSTEKIQKYDNLKYLGTHIQGDAVSYQKLQIRTDKLRTLNDFQKLLGNINWIRPFLKLTTGELKPLFEILNGDSNPISIRKLTPEACKALQLVNERLSIARVKRLDLSRPWSLCILKTEYTPTACLWQNGVLEWIHLPHISPKVITPYDIFCTQLIIKGRHRSKELFSKDPDYIVVPYTKVQFDLLLQEKEDWPISLLGFLGEVHFHLPKDPLLTFTLQTAIIFPHMTSTTPLEKGIVIFTDGSANGRSVTYIQGREPIIKENTQNTAQQAEIVAVITAFEEVSQSFNLYTDSKYVTGLFPEIETATLSPRTKIYTELRHLQRLIHKRQEKFYIGHIRGHTGLPGPLAQGNAYADSLTRILTALESAQESHALHHQNAAALRFQFHITREQAREIVKLCPNCPDWGHAPQLGVNPRGLKPRVLWQMDVTHVSEFGKLKYVHVTVDTYSHFTFATARTGEATKDVLQHLAQSFAYMGFPQKIKTDNAPAYVSRSIQEFLARWKISHVTGIPYNPQGQAIVERTHQNIKAQLNKLQKAGKYYTPHHLLAHALFVLNHVNMDNQGHTAAERHWGPISADPKPMVMWKDLLAGSWKGPDVLITAGRGYACVFPQDAETPIWVPDRFIRPFTERKEATPTPGTAEKTPPRDEKDQQKSPEDESSPHQREDGLATSAGVNLRSGGGS |
| Enzyme Length | 1755 |
| Uniprot Accession Number | P11283 |
| Absorption | |
| Active Site | ACT_SITE 771; /note=Protease; shared with dimeric partner; /evidence=ECO:0000255|PROSITE-ProRule:PRU00275 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | 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}; CATALYTIC ACTIVITY: Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.4; Evidence={ECO:0000255|PROSITE-ProRule:PRU00408}; 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; Evidence={ECO:0000269|PubMed:8091672}; |
| DNA Binding | DNA_BIND 1653..1702; /note=Integrase-type; /evidence=ECO:0000255|PROSITE-ProRule:PRU00506 |
| EC Number | 3.6.1.23; 3.4.23.-; 2.7.7.49; 2.7.7.7; 3.1.26.4; 2.7.7.-; 3.1.-.- |
| Enzyme Function | FUNCTION: [Matrix protein p10]: Matrix protein. {ECO:0000305}.; FUNCTION: Nucleocapsid protein p14: Binds strongly to viral nucleic acids and promote their aggregation. Also destabilizes the nucleic acids duplexes via highly structured zinc-binding motifs. {ECO:0000305}.; FUNCTION: [Capsid protein p27]: Capsid protein. {ECO:0000305}.; FUNCTION: NC-dUTPase has dUTPase activity, thereby preventing incorporation of uracil into DNA. {ECO:0000305|PubMed:8091672}.; 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 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:0000269|PubMed:24124581, ECO:0000303|PubMed:28458055}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (11); Compositional bias (2); DNA binding (1); Domain (4); Initiator methionine (1); Lipidation (1); Metal binding (14); Motif (1); Natural variant (1); Region (3); Sequence conflict (3); Site (8); Zinc finger (3) |
| Keywords | Aspartyl protease;Capsid protein;DNA integration;DNA recombination;DNA-binding;DNA-directed DNA polymerase;Direct protein sequencing;Endonuclease;Hydrolase;Lipoprotein;Magnesium;Metal-binding;Multifunctional enzyme;Myristate;Nuclease;Nucleotide-binding;Nucleotidyltransferase;Phosphoprotein;Protease;RNA-binding;RNA-directed DNA polymerase;Reference proteome;Repeat;Ribosomal frameshifting;Transferase;Viral genome integration;Viral matrix protein;Viral nucleoprotein;Virion;Virus entry into host cell;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Matrix protein p10]: Virion {ECO:0000250|UniProtKB:P10258}.; SUBCELLULAR LOCATION: [Capsid protein p27]: Virion {ECO:0000250|UniProtKB:P10258}.; SUBCELLULAR LOCATION: [Nucleocapsid protein-dUTPase]: Virion {ECO:0000250|UniProtKB:P10258}. |
| Modified Residue | |
| Post Translational Modification | PTM: [Protease]: Released by autocatalytic processing. {ECO:0000250|UniProtKB:P03365}.; PTM: [Gag-Pro-Pol polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins. {ECO:0000269|PubMed:2542570}.; PTM: [Gag-Pro-Pol polyprotein]: Myristoylated. Myristoylation of the matrix (MA) domain mediates the transport and binding of Gag polyproteins to the host plasma membrane and is required for the assembly of viral particles. {ECO:0000269|PubMed:2542570}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | MOTIF 305..308; /note=PTAP/PSAP motif; /evidence=ECO:0000305 |
| Gene Encoded By | |
| Mass | 197,329 |
| Kinetics | |
| Metal Binding | METAL 970; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00405; METAL 1045; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00405; METAL 1046; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00405; METAL 1316; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1346; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1366; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1429; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1445; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00450; METAL 1449; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00450; METAL 1473; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00450; METAL 1476; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00450; METAL 1501; /note=Magnesium 3; catalytic; for integrase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00457; METAL 1558; /note=Magnesium 3; catalytic; for integrase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00457; METAL 1594; /note=Magnesium 3; catalytic; for integrase activity; /evidence=ECO:0000250|UniProtKB:P03354 |
| Rhea ID | RHEA:22508; RHEA:10248 |
| Cross Reference Brenda |