| IED ID | IndEnz0002001844 |
| Enzyme Type ID | protease001844 |
| Protein Name |
Gag-Pol polyprotein Cleaved into: Matrix protein p10 MA ; p20; Capsid protein p25 CA ; Nucleocapsid protein p14 NC-pol ; Protease p15 PR EC 3.4.23.- ; Reverse transcriptase/ribonuclease H p90 RT EC 2.7.7.49 EC 2.7.7.7 EC 3.1.26.4 ; Integrase p46 IN EC 2.7.7.- EC 3.1.-.- |
| Gene Name | gag-pol |
| Organism | Walleye dermal sarcoma virus (WDSV) |
| Taxonomic Lineage | Viruses Riboviria Pararnavirae Artverviricota Revtraviricetes Ortervirales Retroviridae Orthoretrovirinae Epsilonretrovirus Walleye dermal sarcoma virus (WDSV) |
| Enzyme Sequence | MGNSSSTPPPSALKNSDLFKTMLRTQYSGSVKTRRINQDIKKQYPLWPDQGTCATKHWEQAVLIPLDSVSEETAKVLNFLRVKIQARKGETARQMTAHTIKKLIVGTIDKNKQQTEILQKTDESDEEMDTTNTMLFIARNKRERIAQQQQADLAAQQQVLLLQREQQREQREKDIKKRDEKKKKLLPDTTQKVEQTDIGEASSSDASAQKPISTDNNPDLKVDGVLTRSQHTTVPSNITIKKDGTSVQYQHPIRNYPTGEGNLTAQVRNPFRPLELQQLRKDCPALPEGIPQLAEWLTQTMAIYNCDEADVEQLARVIFPTPVRQIAGVINGHAAANTAAKIQNYVTACRQHYPAVCDWGTIQAFTYKPPQTAHEYVKHAEIIFKNNSGLEWQHATVPFINMVVQGLPPKVTRSLMSGNPDWSTKTIPQIIPLMQHYLNLQSRQDAKIKQTPLVLQLAMPAQTMNGNKGYVGSYPTNEPYYSFQQQQRPAPRAPPGNVPSNTCFFCKQPGHWKADCPNKTRNLRNMGNMGRGGRMGGPPYRSQPYPAFIQPPQNHQNQYNGRMDRSQLQASAQEWLPGTYPAXDPIDCPYEKSGTKTTQDVITTKNAEIMVTVNHTKIPMLVDTGACLTAIGGAATVVPDLKLTNTEIIAVGISAEPVPHVLAKPTKIQIENTNIDISPWYNPDQTFHILGRDTLSKMRAIVSFEKNGEMTVLLPPTYHKQLSCQTKNTLNIDEYLLQFPDQLWASLPTDIGRMLVPPITIKIKDNASLPSIRQYPLPKDKTEGLRPLISSLENQGILIKCHSPCNTPIFPIKKAGRDEYRMIHDLRAINNIVAPLTAVVASPTTVLSNLAPSLHWFTVIDLSNAFFSVPIHKDSQYLFAFTFEGHQYTWTVLPQGFIHSPTLFSQALYQSLHKIKFKISSEICIYMDDVLIASKDRDTNLKDTAVMLQHLASEGHKVSKKKLQLCQQEVVYLGQLLTPEGRKILPDRKVTVSQFQQPTTIRQIRAFLGLVGYCRHWIPEFSIHSKFLEKQLKKDTAEPFQLDDQQVEAFNKLKHAITTAPVLVVPDPAKPFQLYTSHSEHASIAVLTQKHAGRTRPIAFLSSKFDAIESGLPPCLKACASIHRSLTQADSFILGAPLIIYTTHAICTLLQRDRSQLVTASRFSKWEADLLRPELTFVACSAVSPAHLYMQSCENNIPPHDCVLLTHTISRPRPDLSDLPIPDPDMTLFSDGSYTTGRGGAAVVMHRPVTDDFIIIHQQPGGASAQTAELLALAAACHLATDKTVNIYTDSRYAYGVVHDFGHLWMHRGFVTSAGTPIKNHKEIEYLLKQIMKPKQVSVIKIEAHTKGVSMEVRGNAAADEAAKNAVFLVQRVLKKGDALASTDLVMEYSETDEKFTAGAELHDGVFMRGDLIVPPLEMLHAILLAIHGVSHTHKGGIMSYFSKFWTHPKASQTIDLILGHCQICLKHNPKYKSRLQGHRPLPSRPFAHLQIDFVQMCVKKPMYALVIIDVFSKWPEIIPCNKEDAKTVCDILMKDIIPRWGLPDQIDSDQGTHFTAKISQELTHSIGVAWKLHCPGHPRSSGIVERTNRTLKSKIIKAQEQLQLSKWTEVLPYVLLEMRATPKKHGLSPHEIVMGRPMKTTYLSDMSPLWATDTLVTYMNKLTRQLSAYHQQVVDQWPSTSLPPGPEPGSWCMLRNPKKSSNWEGPFLILLSTPTAVKVEGRPTWIHLDHCKLLRSSLSSSLGGPVNQLLS |
| Enzyme Length | 1752 |
| Uniprot Accession Number | O92815 |
| Absorption | |
| Active Site | ACT_SITE 623; /note=Protease; shared with dimeric partner; /evidence=ECO:0000250 |
| 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}; |
| DNA Binding | |
| 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 p10]: Targets Gag and gag-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 p25 forms the spherical core of the virion that encapsulates the genomic RNA-nucleocapsid complex. {ECO:0000250}.; FUNCTION: [Nucleocapsid protein p14]: Involved in the packaging and encapsidation of two copies of the genome. Binds with high affinity to conserved UCUG elements within the packaging signal, located near the 5'-end of the genome. This binding is dependent on genome dimerization (By similarity). {ECO:0000250}.; FUNCTION: [Protease p15]: 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 (By similarity). {ECO:0000250}.; FUNCTION: [Reverse transcriptase/ribonuclease H p90]: 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 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 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 (By similarity). {ECO:0000250}.; FUNCTION: [Integrase p46]: 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 CA OH's at the 3' ends. In the second step that requires cell division, the PIC enters cell nucleus. 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. The last step is viral DNA integration into host chromosome. {ECO:0000269|PubMed:24124581}.; FUNCTION: [Gag-Pol polyprotein]: Plays a role in budding and is processed by the viral protease during virion maturation outside the cell. {ECO:0000250}. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.0 for protease p14.; |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (8); Coiled coil (1); Compositional bias (2); Domain (4); Initiator methionine (1); Lipidation (1); Metal binding (9); Region (2); Site (6); Zinc finger (1) |
| Keywords | Aspartyl protease;Capsid protein;Coiled coil;DNA integration;DNA recombination;DNA-binding;DNA-directed DNA polymerase;Direct protein sequencing;Endonuclease;Host cell membrane;Host membrane;Hydrolase;Lipoprotein;Magnesium;Membrane;Metal-binding;Multifunctional enzyme;Myristate;Nuclease;Nucleotidyltransferase;Phosphoprotein;Protease;RNA suppression of termination;RNA-binding;RNA-directed DNA polymerase;Reference proteome;Transferase;Viral matrix protein;Viral nucleoprotein;Virion;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}.; SUBCELLULAR LOCATION: [Matrix protein p10]: 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: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation (By similarity). {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 196,265 |
| Kinetics | |
| Metal Binding | METAL 861; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000250; METAL 928; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000250; METAL 929; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000250; METAL 1231; /note=Magnesium; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1269; /note=Magnesium; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1290; /note=Magnesium; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1360; /note=Magnesium; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1493; /note=Magnesium 3; catalytic; for integrase activity; /evidence=ECO:0000250; METAL 1550; /note=Magnesium 3; catalytic; for integrase activity; /evidence=ECO:0000250 |
| Rhea ID | RHEA:22508 |
| Cross Reference Brenda |