| IED ID | IndEnz0002001311 |
| Enzyme Type ID | protease001311 |
| Protein Name |
Gag-Pol polyprotein Cleaved into: Matrix protein p15 MA ; RNA-binding phosphoprotein p12 pp12 ; Capsid protein p30 CA ; Nucleocapsid protein p10-Pol NC-pol ; 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 | pol |
| Organism | AKV murine leukemia virus (AKR (endogenous) murine leukemia virus) |
| Taxonomic Lineage | Viruses Riboviria Pararnavirae Artverviricota Revtraviricetes Ortervirales Retroviridae Orthoretrovirinae Gammaretrovirus Murine leukemia virus AKV murine leukemia virus (AKR (endogenous) murine leukemia virus) |
| Enzyme Sequence | MGQTVTTPLSLTLEHWEDVQRIASNQSVDVKKRRWVTFCSAEWPTFGVGWPQDGTFNLDIILQVKSKVFSPGPHGHPDQVPYIVTWEAIAYEPPPWVKPFVSPKLSPSPTAPILPSGPSTQPPPRSALYPALTPSIKPRPSKPQVLSDNGGPLIDLLSEDPPPYGGQGLSSSDGDGDREEATSTSEIPAPSPIVSRLRGKRDPPAADSTTSRAFPLRLGGNGQLQYWPFSSSDLYNWKNNNPSFSEDPGKLTALIESVLTTHQPTWDDCQQLLGTLLTGEEKQRVLLEARKAVRGNDGRPTQLPNEVDAAFPLERPDWDYTTQRGRNHLVLYRQLLLAGLQNAGRSPTNLAKVKGITQGPNESPSAFLERLKEAYRRYTPYDPEDPGQETNVSMSFIWQSAPDIGRKLERLEDLKSKTLGDLVREAERIFNKRETPEEREERVRRETEEKEERRRAEEEQKEKERDRRRHREMSKLLATVVSGQRQDRQGGERRRPQLDKDQCAYCKEKGHWAKDCPKKPRGPRGPRPQTSLLTLDDQGGQGQEPPPEPRITLTVGGQPVTFLVDTGAQHSVLTQNPGPLSDRSAWVQGATGGKRYRWTTDRKVHLATGKVTHSFLHVPDCPYPLLGRDLLTKLKAQIHFEGSGAQVVGPKGQPLQVLTLNLEDEYRLYETSAEPEVSPGSTWLSDFPQAWAETGGMGLAVRQAPLIIPLKATSTPVSIKQYPMSQEAKLGIKPHIQRLLDQGILVPCQSPWNTPLLPVKKPGTNDYRPVQDLREVNKRVEDIHPTVPNPYNLLSGLPPSHRWYTVLDLKDAFFCLRLHPTSQPLFAFEWRDPGMGISGQLTWTRLPQGFKNSPTLFDEALHRDLADFRIQHPDLILLQYVDDILLAATSELDCQQGTRALLLTLGNLGYRASAKKAQLCQKQVKYLGYLLKEGQRWLTEARKETVMGQPTPKTPRQLREFLGTAGFCRLWIPGFAEMAAPLYPLTKTGTLFNWGPDQQKAYQEIKQALLTAPALGLPDLTKPFELFVDEKQGYAKGVLTQKLGPWRRPVAYLSKKLDPVAAGWPPCLRMVAAIAVLRKDAGKLTMGQPLVILAPHAVEALVKQPPDRWLSNARMTHYQAMLLDTDRVQFGPVVALNPATLLPLPEEGAPHDCLEILAETHGTRPDLTDQPIPDADHTWYTDGSSFLQEGQRKAGAAVTTETEVIWARALPAGTSAQRAELIALTQALKMAEGKRLNVYTDSRYAFATAHIHGEIYRRRGLLTSEGREIKNKSEILALLKALFLPKRLSIIHCLGHQKGDSAEARGNRLADQAAREAAIKTPPDTSTLLIEDSTPYTPAYFHYTETDLKKLRELGATYNQSKGYWVFQGKPVMPDQFVFELLDSLHRLTHLGYQKMKALLDRGESPYYMLNRDKTLQYVADSCTVCAQVNASKAKIGAGVRVRGHRPGSHWEIDFTEVKPGLYGYKYLLVFVDTFSGWVEAFPTKRETARVVSKKLLEEIFPRFGMPQVLGSDNGPAFTSQVSQSVADLLGIDWKLHCAYRPQSSGQVERMNRTIKETLTKLTLAAGTRDWVLLLPLALYRARNTPGPHGLTPYEILYGAPPPLVNFHDPDMSELTNSPSLQAHLQALQTVQREIWKPLAEAYRDQLDQPVIPHPFRIGDSVWVRRHQTKNLEPRWKGPYTVLLTTPTALKVDGISAWIHAAHVKAATTPPIKPSWRVQRSQNPLKIRLTRGAP |
| Enzyme Length | 1734 |
| Uniprot Accession Number | P03356 |
| Absorption | |
| Active Site | ACT_SITE 565; /note=Protease; shared with dimeric partner; /evidence=ECO:0000255|PROSITE-ProRule:PRU00275 |
| Activity Regulation | ACTIVITY REGULATION: [Protease]: Most efficiently inhibited by Amprenavir, which is able to block Gag-Pol processing in infected cells. {ECO:0000250|UniProtKB:P03355}. |
| 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: [Gag-Pol polyprotein]: Plays a role in budding and is processed by the viral protease during virion maturation outside the cell. During budding, it recruits, in a PPXY-dependent or independent manner, Nedd4-like ubiquitin ligases that conjugate ubiquitin molecules to Gag-Pol, or to Gag-Pol binding host factors. Interaction with HECT ubiquitin ligases probably link the viral protein to the host ESCRT pathway and facilitates release. {ECO:0000250|UniProtKB:P03332}.; FUNCTION: [Matrix protein p15]: 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 pre-integration complex. {ECO:0000250|UniProtKB:P03332}.; FUNCTION: [RNA-binding phosphoprotein p12]: Constituent of the pre-integration complex (PIC) which tethers the latter to mitotic chromosomes. This allows the integration of the viral genome into the host DNA. {ECO:0000250|UniProtKB:P03355}.; FUNCTION: [Capsid protein p30]: Forms the spherical core of the virion that encapsulates the genomic RNA-nucleocapsid complex. {ECO:0000250|UniProtKB:P03336}.; FUNCTION: [Nucleocapsid protein p10-Pol]: 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. Acts as a nucleic acid chaperone which is involved in rearrangement of nucleic acid secondary structures during gRNA retrotranscription (By similarity). {ECO:0000250|UniProtKB:P03332, ECO:0000250|UniProtKB:P03355}.; 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 (Potential). Cleaves the translation initiation factor eIF4G leading to the inhibition of host cap-dependent translation (By similarity). {ECO:0000250|UniProtKB:P03332, 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 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. {ECO:0000255}.; 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 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:0000250|UniProtKB:P03355}. |
| Temperature Dependency | |
| PH Dependency | |
| 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); Modified residue (1); Motif (3); Region (5); Sequence conflict (2); Site (6); Zinc finger (2) |
| Keywords | Aspartyl protease;Capsid protein;Coiled coil;DNA integration;DNA recombination;DNA-binding;DNA-directed DNA polymerase;Endonuclease;Eukaryotic host gene expression shutoff by virus;Eukaryotic host translation shutoff by virus;Host cell membrane;Host cytoplasm;Host endosome;Host gene expression shutoff by virus;Host membrane;Host-virus interaction;Hydrolase;Lipoprotein;Magnesium;Membrane;Metal-binding;Multifunctional enzyme;Myristate;Nuclease;Nucleotidyltransferase;Phosphoprotein;Protease;RNA suppression of termination;RNA-binding;RNA-directed DNA polymerase;Transferase;Ubl conjugation;Viral genome integration;Viral matrix protein;Viral nucleoprotein;Virion;Virus entry into host cell;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Virion {ECO:0000250|UniProtKB:P03332}. Host cell membrane {ECO:0000250|UniProtKB:P03332}; Lipid-anchor {ECO:0000250|UniProtKB:P03332}. Host late endosome membrane {ECO:0000250|UniProtKB:P03332}; Lipid-anchor {ECO:0000250|UniProtKB:P03332}. Host endosome, host multivesicular body {ECO:0000250|UniProtKB:P26807}. Note=These locations are probably linked to virus assembly sites. {ECO:0000250|UniProtKB:P03355}.; SUBCELLULAR LOCATION: [Matrix protein p15]: Virion {ECO:0000250|UniProtKB:P03355}.; SUBCELLULAR LOCATION: [Capsid protein p30]: Virion {ECO:0000250|UniProtKB:P03355}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p10-Pol]: Virion {ECO:0000250|UniProtKB:P03355}.; SUBCELLULAR LOCATION: [Protease]: Virion {ECO:0000250|UniProtKB:P03355}.; SUBCELLULAR LOCATION: [RNA-binding phosphoprotein p12]: Host cytoplasm {ECO:0000250|UniProtKB:P03355}. Note=Localizes to the host cytoplasm early in infection and binds to the mitotic chromosomes later on. {ECO:0000250|UniProtKB:P03355}. |
| Modified Residue | MOD_RES 191; /note=Phosphoserine; by host; /evidence=ECO:0000250|UniProtKB:P03355 |
| Post Translational Modification | PTM: [Gag-Pol polyprotein]: Ubiquitinated by ITCH. Gag can recruit the ubiquitin ligase Itch in an L domain-independent manner to facilitate virus release via a mechanism that involves Gag ubiquitination. {ECO:0000250|UniProtKB:P03332}.; PTM: [Gag-Pol polyprotein]: 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. {ECO:0000250|UniProtKB:P03355}.; PTM: [Capsid protein p30]: Sumoylated; which is required for virus replication. {ECO:0000250|UniProtKB:P03355}.; PTM: [RNA-binding phosphoprotein p12]: Phosphorylated on serine residues. {ECO:0000250|UniProtKB:P03355}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | MOTIF 109..112; /note=PTAP/PSAP motif; /evidence=ECO:0000250|UniProtKB:P03332; MOTIF 128..132; /note=LYPX(n)L motif; /evidence=ECO:0000250|UniProtKB:P03332; MOTIF 161..164; /note=PPXY motif; /evidence=ECO:0000250|UniProtKB:P03332 |
| Gene Encoded By | |
| Mass | 194,081 |
| Kinetics | |
| Metal Binding | METAL 808; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00405; METAL 882; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00405; METAL 883; /note=Magnesium 1; catalytic; for reverse transcriptase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00405; METAL 1182; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1220; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1241; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1311; /note=Magnesium 2; catalytic; for RNase H activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00408; METAL 1454; /note=Magnesium 3; catalytic; for integrase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00457; METAL 1513; /note=Magnesium 3; catalytic; for integrase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00457 |
| Rhea ID | RHEA:22508 |
| Cross Reference Brenda |