UniProt functional annotation for P03366



	UniProt functional annotation for P03366

UniProt codes: P03366, P03368.

Organism: Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1).

Taxonomy: Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes; Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.

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}.

Function: [Reverse transcriptase/ribonuclease H]: 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(3)-Lys 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 two polypurine tracts (PPTs) situated at the 5'-end and near the center 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 PPTs that have not been removed by RNase H as primers. PPTs 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:0000250|UniProtKB:P04585}.

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, Vpr 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, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. 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 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 are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration. {ECO:0000250|UniProtKB:P04585}.

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};

Catalytic activity: Reaction=3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.; EC=3.1.13.2; Evidence={ECO:0000250};

Catalytic activity: [Reverse transcriptase/ribonuclease H]: Reaction=Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.; EC=3.1.26.13; Evidence={ECO:0000269|PubMed:2476069};

Catalytic activity: [Reverse transcriptase/ribonuclease H]: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:11130, Rhea:RHEA-COMP:11131, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:83828; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE- ProRule:PRU00405, ECO:0000269|PubMed:2476069};

Catalytic activity: [Reverse transcriptase/ribonuclease H]: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:11130, Rhea:RHEA-COMP:11131, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:83828; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE- ProRule:PRU00405, ECO:0000269|PubMed:2476069};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for reverse transcriptase polymerase activity. {ECO:0000250};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding. {ECO:0000250};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions. {ECO:0000250};

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. Reverse transcriptase/ribonuclease H: RT can be inhibited either by nucleoside RT inhibitors (NRTIs) or by non nucleoside RT inhibitors (NNRTIs). NRTIs act as chain terminators, whereas NNRTIs inhibit DNA polymerization by binding a small hydrophobic pocket near the RT active site and inducing an allosteric change in this region. Classical NRTIs are abacavir, adefovir (PMEA), didanosine (ddI), lamivudine (3TC), stavudine (d4T), tenofovir (PMPA), zalcitabine (ddC), and zidovudine (AZT). Classical NNRTIs are atevirdine (BHAP U-87201E), delavirdine, efavirenz (DMP-266), emivirine (I-EBU), and nevirapine (BI-RG-587). The tritherapies used as a basic effective treatment of AIDS associate two NRTIs and one NNRTI. {ECO:0000250}.

Subunit: [Matrix protein p17]: Homotrimer; further assembles as hexamers of trimers (By similarity). Interacts with gp41 (via C- terminus) (By similarity). Interacts with host CALM1; this interaction induces a conformational change in the Matrix protein, triggering exposure of the myristate group (By similarity). Interacts with host AP3D1; this interaction allows the polyprotein trafficking to multivesicular bodies during virus assembly (By similarity). Part of the pre-integration complex (PIC) which is composed of viral genome, matrix protein, Vpr and integrase (By similarity). {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.

Subunit: [Capsid protein p24]: Homodimer; the homodimer further multimerizes as homohexamers or homopentamers. Interacts with human PPIA/CYPA (By similarity); This interaction stabilizes the capsid. Interacts with human NUP153 (By similarity). Interacts with host PDZD8; this interaction stabilizes the capsid (By similarity). Interacts with monkey TRIM5; this interaction destabilizes the capsid (By similarity). {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.

Subunit: [Protease]: Homodimer, whose active site consists of two apposed aspartic acid residues. {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.

Subunit: [Reverse transcriptase/ribonuclease H]: Heterodimer of p66 RT and p51 RT (RT p66/p51) (PubMed:8805568, PubMed:7687065). Heterodimerization of RT is essential for DNA polymerase activity (PubMed:8805568, PubMed:7687065). The overall folding of the subdomains is similar in p66 RT and p51 RT but the spatial arrangements of the subdomains are dramatically different (PubMed:7687065). {ECO:0000269|PubMed:7687065, ECO:0000269|PubMed:8805568}.

Subunit: [Integrase]: Homotetramer; may further associate as a homohexadecamer (By similarity). Part of the pre-integration complex (PIC) which is composed of viral genome, matrix protein, Vpr and integrase. Interacts with human SMARCB1/INI1 and human PSIP1/LEDGF isoform 1. Interacts with human KPNA3; this interaction might play a role in nuclear import of the pre-integration complex (By similarity). Interacts with human NUP153; this interaction might play a role in nuclear import of the pre-integration complex (By similarity). {ECO:0000250|UniProtKB:P03367, ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.

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}.

Subcellular location: [Reverse transcriptase/ribonuclease H]: Virion {ECO:0000305}.

Subcellular location: [Integrase]: Virion {ECO:0000305}. Host nucleus {ECO:0000305}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.

Domain: [Reverse transcriptase/ribonuclease H]: RT is structured in five subdomains: finger, palm, thumb, connection and RNase H. Within the palm subdomain, the 'primer grip' region is thought to be involved in the positioning of the primer terminus for accommodating the incoming nucleotide. The RNase H domain stabilizes the association of RT with primer-template. {ECO:0000250}.

Domain: [Reverse transcriptase/ribonuclease H]: The tryptophan repeat motif is involved in RT p66/p51 dimerization (By similarity). {ECO:0000250}.

Domain: [Integrase]: The core domain contains the D-x(n)-D-x(35)-E motif, named for the phylogenetically conserved glutamic acid and aspartic acid residues and the invariant 35 amino acid spacing between the second and third acidic residues. Each acidic residue of the D,D(35)E motif is independently essential for the 3'-processing and strand transfer activities of purified integrase protein. {ECO:0000250}.

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. 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. {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00405}.

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:P12497}.

Ptm: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000269|PubMed:17415034}.

Miscellaneous: [Reverse transcriptase/ribonuclease H]: Error-prone enzyme that lacks a proof-reading function. High mutations rate is a direct consequence of this characteristic. RT also displays frequent template switching leading to high recombination rate. Recombination mostly occurs between homologous regions of the two copackaged RNA genomes. If these two RNA molecules derive from different viral strains, reverse transcription will give rise to highly recombinated proviral DNAs. {ECO:0000250}.

Miscellaneous: HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).

Miscellaneous: Resistance to inhibitors associated with mutations are observed both in viral protease and in reverse transcriptase. Most of the time, single mutations confer only a modest reduction in drug susceptibility. Combination of several mutations is usually required to develop a high-level drug resistance. These mutations are predominantly found in clade B viruses and not in other genotypes. They are listed in the clade B representative isolate HXB2 (AC P04585).

Miscellaneous: [Isoform Gag-Pol polyprotein]: Produced by -1 ribosomal frameshifting.

Annotations taken from UniProtKB at the EBI.


Organism:		Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1).
Taxonomy:		Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes; Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.



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}.



Function:		[Reverse transcriptase/ribonuclease H]: 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(3)-Lys 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 two polypurine tracts (PPTs) situated at the 5'-end and near the center 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 PPTs that have not been removed by RNase H as primers. PPTs 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:0000250\|UniProtKB:P04585}.



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, Vpr 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, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. 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 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 are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration. {ECO:0000250\|UniProtKB:P04585}.


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};
Catalytic activity:		Reaction=3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.; EC=3.1.13.2; Evidence={ECO:0000250};
Catalytic activity:		[Reverse transcriptase/ribonuclease H]: Reaction=Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.; EC=3.1.26.13; Evidence={ECO:0000269\|PubMed:2476069};
Catalytic activity:		[Reverse transcriptase/ribonuclease H]: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:11130, Rhea:RHEA-COMP:11131, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:83828; EC=2.7.7.49; Evidence={ECO:0000255\|PROSITE- ProRule:PRU00405, ECO:0000269\|PubMed:2476069};
Catalytic activity:		[Reverse transcriptase/ribonuclease H]: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:11130, Rhea:RHEA-COMP:11131, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:83828; EC=2.7.7.7; Evidence={ECO:0000255\|PROSITE- ProRule:PRU00405, ECO:0000269\|PubMed:2476069};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for reverse transcriptase polymerase activity. {ECO:0000250};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding. {ECO:0000250};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions. {ECO:0000250};
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. Reverse transcriptase/ribonuclease H: RT can be inhibited either by nucleoside RT inhibitors (NRTIs) or by non nucleoside RT inhibitors (NNRTIs). NRTIs act as chain terminators, whereas NNRTIs inhibit DNA polymerization by binding a small hydrophobic pocket near the RT active site and inducing an allosteric change in this region. Classical NRTIs are abacavir, adefovir (PMEA), didanosine (ddI), lamivudine (3TC), stavudine (d4T), tenofovir (PMPA), zalcitabine (ddC), and zidovudine (AZT). Classical NNRTIs are atevirdine (BHAP U-87201E), delavirdine, efavirenz (DMP-266), emivirine (I-EBU), and nevirapine (BI-RG-587). The tritherapies used as a basic effective treatment of AIDS associate two NRTIs and one NNRTI. {ECO:0000250}.
Subunit:		[Matrix protein p17]: Homotrimer; further assembles as hexamers of trimers (By similarity). Interacts with gp41 (via C- terminus) (By similarity). Interacts with host CALM1; this interaction induces a conformational change in the Matrix protein, triggering exposure of the myristate group (By similarity). Interacts with host AP3D1; this interaction allows the polyprotein trafficking to multivesicular bodies during virus assembly (By similarity). Part of the pre-integration complex (PIC) which is composed of viral genome, matrix protein, Vpr and integrase (By similarity). {ECO:0000250\|UniProtKB:P04585, ECO:0000250\|UniProtKB:P12497}.
Subunit:		[Capsid protein p24]: Homodimer; the homodimer further multimerizes as homohexamers or homopentamers. Interacts with human PPIA/CYPA (By similarity); This interaction stabilizes the capsid. Interacts with human NUP153 (By similarity). Interacts with host PDZD8; this interaction stabilizes the capsid (By similarity). Interacts with monkey TRIM5; this interaction destabilizes the capsid (By similarity). {ECO:0000250\|UniProtKB:P04585, ECO:0000250\|UniProtKB:P12497}.
Subunit:		[Protease]: Homodimer, whose active site consists of two apposed aspartic acid residues. {ECO:0000250\|UniProtKB:P04585, ECO:0000250\|UniProtKB:P12497}.
Subunit:		[Reverse transcriptase/ribonuclease H]: Heterodimer of p66 RT and p51 RT (RT p66/p51) (PubMed:8805568, PubMed:7687065). Heterodimerization of RT is essential for DNA polymerase activity (PubMed:8805568, PubMed:7687065). The overall folding of the subdomains is similar in p66 RT and p51 RT but the spatial arrangements of the subdomains are dramatically different (PubMed:7687065). {ECO:0000269\|PubMed:7687065, ECO:0000269\|PubMed:8805568}.
Subunit:		[Integrase]: Homotetramer; may further associate as a homohexadecamer (By similarity). Part of the pre-integration complex (PIC) which is composed of viral genome, matrix protein, Vpr and integrase. Interacts with human SMARCB1/INI1 and human PSIP1/LEDGF isoform 1. Interacts with human KPNA3; this interaction might play a role in nuclear import of the pre-integration complex (By similarity). Interacts with human NUP153; this interaction might play a role in nuclear import of the pre-integration complex (By similarity). {ECO:0000250\|UniProtKB:P03367, ECO:0000250\|UniProtKB:P04585, ECO:0000250\|UniProtKB:P12497}.
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}.
Subcellular location:		[Reverse transcriptase/ribonuclease H]: Virion {ECO:0000305}.
Subcellular location:		[Integrase]: Virion {ECO:0000305}. Host nucleus {ECO:0000305}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.
Domain:		[Reverse transcriptase/ribonuclease H]: RT is structured in five subdomains: finger, palm, thumb, connection and RNase H. Within the palm subdomain, the 'primer grip' region is thought to be involved in the positioning of the primer terminus for accommodating the incoming nucleotide. The RNase H domain stabilizes the association of RT with primer-template. {ECO:0000250}.
Domain:		[Reverse transcriptase/ribonuclease H]: The tryptophan repeat motif is involved in RT p66/p51 dimerization (By similarity). {ECO:0000250}.
Domain:		[Integrase]: The core domain contains the D-x(n)-D-x(35)-E motif, named for the phylogenetically conserved glutamic acid and aspartic acid residues and the invariant 35 amino acid spacing between the second and third acidic residues. Each acidic residue of the D,D(35)E motif is independently essential for the 3'-processing and strand transfer activities of purified integrase protein. {ECO:0000250}.
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. 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. {ECO:0000250\|UniProtKB:P04585, ECO:0000255\|PROSITE-ProRule:PRU00405}.
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:P12497}.
Ptm:		[Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000269\|PubMed:17415034}.
Miscellaneous:		[Reverse transcriptase/ribonuclease H]: Error-prone enzyme that lacks a proof-reading function. High mutations rate is a direct consequence of this characteristic. RT also displays frequent template switching leading to high recombination rate. Recombination mostly occurs between homologous regions of the two copackaged RNA genomes. If these two RNA molecules derive from different viral strains, reverse transcription will give rise to highly recombinated proviral DNAs. {ECO:0000250}.
Miscellaneous:		HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).
Miscellaneous:		Resistance to inhibitors associated with mutations are observed both in viral protease and in reverse transcriptase. Most of the time, single mutations confer only a modest reduction in drug susceptibility. Combination of several mutations is usually required to develop a high-level drug resistance. These mutations are predominantly found in clade B viruses and not in other genotypes. They are listed in the clade B representative isolate HXB2 (AC P04585).
Miscellaneous:		[Isoform Gag-Pol polyprotein]: Produced by -1 ribosomal frameshifting.