| IED ID | IndEnz0002011741 |
| Enzyme Type ID | protease011741 |
| Protein Name |
Gag-Pol polyprotein Pr160Gag-Pol Cleaved into: Matrix protein p17 MA ; Capsid protein p24 CA ; Spacer peptide 1 SP1 p2 ; Nucleocapsid protein p7 NC ; Transframe peptide TF ; p6-pol p6* ; Protease EC 3.4.23.16 PR Retropepsin Fragment |
| Gene Name | gag-pol |
| Organism | Human immunodeficiency virus type 1 group M subtype B (isolate CDC-451) (HIV-1) |
| Taxonomic Lineage | Viruses Riboviria Pararnavirae Artverviricota Revtraviricetes Ortervirales Retroviridae Orthoretrovirinae Lentivirus Human immunodeficiency virus 1 HIV-1 unknown group Human immunodeficiency virus type 1 group M subtype B (isolate CDC-451) (HIV-1) |
| Enzyme Sequence | MGARASVLSGGELDRWEKIRLRPGGKKQYRLKHIVWASRKLERFAVNPGLLETSKGCRQILGQLQPSLQTGSEELRSLYNTVATLYCVHQRIEVRDTKEALDKIEEEQNKSKKKAQQAAADTGNSSQVSQNYPIVQNLQGQMVHQAISPRTLNAWVKVIEEKAFSPEVIPMFAALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRLHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPTPVGEIYKRWIILGLNKIVRMYSPISILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVLAEAMSQVTNSATIMMQRGNFRRQGKTVKCFNCGKEGHIARNCKAPRKKGCWKCGREGHQMKDCTERQANFLREDLAFPQGKAREFSSEQTRANSPTRGELQVWGRDNNSLSEAGAERQGTVSFSFPQITLWQRPIVTIKIGGQLKEALLDTGADDTVLEEINLPGRWKPKMIGGIGGFIKVRQYDEV |
| Enzyme Length | 550 |
| Uniprot Accession Number | P05960 |
| Absorption | |
| Active Site | ACT_SITE 513; /note=For protease activity; shared with dimeric partner; /evidence=ECO:0000255|PROSITE-ProRule:PRU10094 |
| Activity Regulation | ACTIVITY REGULATION: [Protease]: The viral protease is inhibited by many synthetic protease inhibitors (PIs), such as amprenavir, atazanavir, indinavir, loprinavir, nelfinavir, ritonavir and saquinavir. Use of protease inhibitors in tritherapy regimens permit more ambitious therapeutic strategies. {ECO:0000250}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.; EC=3.4.23.16; Evidence={ECO:0000255|PROSITE-ProRule:PRU00275}; |
| DNA Binding | |
| EC Number | 3.4.23.16 |
| 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 (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation. {ECO:0000250}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA. {ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating. On the other hand, interactions with PDZD8 or CYPA stabilize the capsid. {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Nucleocapsid protein p7]: 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 rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Protease]: Aspartyl protease that 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. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 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. Also mediates cleavage of host YTHDF3. Mediates cleavage of host CARD8, thereby activating the CARD8 inflammasome, leading to the clearance of latent HIV-1 in patient CD4(+) T-cells after viral reactivation; in contrast, HIV-1 can evade CARD8-sensing when its protease remains inactive in infected cells prior to viral budding (By similarity). {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00275}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (6); Compositional bias (1); Domain (1); Initiator methionine (1); Lipidation (1); Modified residue (1); Motif (2); Non-terminal residue (1); Peptide (2); Region (11); Site (7); Zinc finger (2) |
| Keywords | AIDS;Aspartyl protease;Capsid protein;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 nucleus;Host-virus interaction;Hydrolase;Lipid-binding;Lipoprotein;Membrane;Metal-binding;Myristate;Phosphoprotein;Protease;RNA-binding;Repeat;Ribosomal frameshifting;Viral nucleoprotein;Viral release from host cell;Virion;Virion maturation;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane; Lipid-anchor. Host endosome, host multivesicular body. Note=These locations are linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12497}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane; Lipid-anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000305}. |
| Modified Residue | MOD_RES 132; /note=Phosphotyrosine; by host; /evidence=ECO:0000250 |
| 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. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry (By similarity). {ECO:0000250}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04585}.; PTM: [Capsid protein p24]: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | MOTIF 16..22; /note=Nuclear export signal; /evidence=ECO:0000250; MOTIF 26..32; /note=Nuclear localization signal; /evidence=ECO:0000250 |
| Gene Encoded By | |
| Mass | 61,404 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |