| IED ID | IndEnz0002011520 |
| Enzyme Type ID | protease011520 |
| Protein Name |
Gag-Pro-Pol polyprotein Pr160Gag-Pro-Pol Cleaved into: Matrix protein p19 MA ; Capsid protein p24 CA ; Nucleocapsid protein p15-pro NC' NC-pro ; Protease PR EC 3.4.23.- ; p1; 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 | Human T-cell leukemia virus 3 (strain 2026ND) (HTLV-3) |
| Taxonomic Lineage | Viruses Riboviria Pararnavirae Artverviricota Revtraviricetes Ortervirales Retroviridae Orthoretrovirinae Deltaretrovirus Primate T-lymphotropic virus 3 Human T-cell leukemia virus 3 (HTLV-3) (Human T-lymphotropic virus 3) Human T-cell leukemia virus 3 (strain 2026ND) (HTLV-3) |
| Enzyme Sequence | MGKTYSSPINPIPKAPKGLAIHHWLNFLQAAYRLQPGPSEFDFHQLRKFLKLAIKTPVWLNPINYSVLAGLIPKNYPGRVHEIVAILIQETPAREAPPSAPLAEDPQKPPPYPEQAQEASQCLPILHPHGAPAAHRPWQMKDLQAIKQEVSSSAPGSPQFMQTIRLAVQQFDPTAKDLHDLLQYLCSSLVASLHHQQLETLIAQAETQGITGYNPLAGPLRIQANNPNQQGLRKEYQNLWLSAFSALPGNTKDPTWAAILQGPEEPFGSFVERLNVALDNGLPEGTPKDPILRSLAYSNANKECQKLLQARGQTNSPLGEMLRACQTWTPRDKNKILMVQPKKTPPPNQPCFRCGQVGHWSRDCKQPRPPPGPCPVCQDPTHWKRDCPQLKTDTRDSEDLLLDLPCEAPNVRERKNLLRGGGLASPRTILPLIPLSQQKQPTLHIQVSFSNTPPVSVQALLDTGADITVLPACLCPPDSNLQDTTVLGAGGPSTNKFKILPCPVHIHLPFRRQPVTLTACLIDINNQWTILGRDALQQCQSSLYLADQPSKVLPVLAPKLIGLEHLPPPPEVSQFPLNPERLQALTDLVSRALEAKHIEPYQGPGNNPIFPVKKPNGKWRFIHDLRATNSVTRDLASPSPGPPDLTSLPQGLPHLRTIDLTDAFFQIPLPTIFQPYFAFTLPQPNNYGPGTRYSWRVLPQGFKNSPTLFEQQLSHILTPVRKTFPNSLIIQYMDDILLASPAPGELAALTDKVTNALTKEGLPLSPEKTQATPGPIHFLGQVISQDCITYETLPSINVKSTWSLAELQSMLGELQWVSKGTPVLRSSLHQLYLALRGHRDPRDTIKLTSIQVQALRTIQKALTLNCRSRLVNQLPILALIMLRPTGTTAVLFQTKQKWPLVWLHTPHPATSLRPWGQLLANAVIILDKYSLQHYGQVCKSFHHNISNQALTYYLHTSDQSSVAILLQHSHRFHNLGAQPSGPWRSLLQMPQIFQNIDVLRPPFTISPVVINHAPCLFSDGSASKAAFIIWDRQVIHQQVLSLPSTCSAQAGELFGLLAGLQKSQPWVALNIFLDSKFLIGHLRRMALGAFPGPSTQCELHTQLLPLLQGKTVYVHHVRSHTLLQDPISRLNEATDALMLAPLLPLDPTTLHQLTHCNPYALRNHGATASEAHAIVQACHTCKVINPQGRLPQGYIRRGHAPNDIWQGDVTHLQYKRYKYCLLVWVDTYSGAVSVSCRRKETGSDCVASLLVAISILGKPQNINTDNGAAYLSQEFQQFCNSLAIKHSTHIPYNPTSSGLVERTNGILKTLISKYLLDNHHLPLETAVSKSLWTINHLNVLPSCQKTRWQLHQAQPLPPVPEDTLPPHTSPKWYYYKIPGLTNSRWSGPVQSLKEAAGAALIPVGGSYLWIPWRLLKRGICPRPESSAAVDPKTRDHQLHG |
| Enzyme Length | 1440 |
| Uniprot Accession Number | Q0R5R2 |
| Absorption | |
| Active Site | ACT_SITE 462; /note=For protease activity; shared with dimeric partner; /evidence=ECO:0000255|PROSITE-ProRule:PRU10094 |
| 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 | DNA_BIND 1371..1420; /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; 2.7.7.-; 3.1.-.- |
| Enzyme Function | FUNCTION: Matrix protein p19 targets Gag, Gag-Pro and Gag-Pro-Pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex (By similarity). {ECO:0000250}.; FUNCTION: Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex. {ECO:0000250}.; FUNCTION: Nucleocapsid protein p15 is involved in the packaging and encapsidation of two copies of the genome. {ECO:0000250}.; FUNCTION: The aspartyl protease mediates proteolytic cleavages of Gag, Gag-Pro and Gag-Pro-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. Hydrolyzes host EIF4GI in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (By similarity). {ECO:0000250}.; FUNCTION: Reverse transcriptase (RT) is a multifunctional enzyme that converts the viral 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-Pro 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 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 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, leaving recessed dinucleotides OH's at the 3' ends. 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). {ECO:0000250}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (7); DNA binding (1); Domain (4); Initiator methionine (1); Lipidation (1); Metal binding (9); Motif (2); Peptide (1); Region (1); Site (6); Zinc finger (2) |
| Keywords | Aspartyl protease;Capsid protein;DNA integration;DNA recombination;DNA-binding;Endonuclease;Eukaryotic host gene expression shutoff by virus;Eukaryotic host translation shutoff by virus;Host gene expression shutoff by virus;Host-virus interaction;Hydrolase;Lipoprotein;Magnesium;Metal-binding;Multifunctional enzyme;Myristate;Nuclease;Nucleotidyltransferase;Protease;RNA-directed DNA polymerase;Reference proteome;Repeat;Ribosomal frameshifting;Transferase;Viral genome integration;Viral nucleoprotein;Virion;Virus entry into host cell;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Matrix protein p19]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p15-pro]: Virion {ECO:0000305}. |
| Modified Residue | |
| Post Translational Modification | PTM: Specific enzymatic cleavages by the viral protease yield mature proteins. The polyprotein is cleaved during and after budding, this process is termed maturation. The protease is autoproteolytically processed at its N- and C-termini (By similarity). {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | MOTIF 98..101; /note=PTAP/PSAP motif; MOTIF 109..112; /note=PPXY motif |
| Gene Encoded By | |
| Mass | 159,835 |
| Kinetics | |
| Metal Binding | METAL 659; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000250; METAL 734; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000250; METAL 735; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000250; METAL 1019; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000250; METAL 1052; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000250; METAL 1074; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000250; METAL 1135; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000250; METAL 1208; /note=Magnesium 3; catalytic; for integrase activity; /evidence=ECO:0000250; METAL 1265; /note=Magnesium 3; catalytic; for integrase activity; /evidence=ECO:0000250 |
| Rhea ID | RHEA:22508 |
| Cross Reference Brenda |