POL_HV1A2
ID POL_HV1A2 Reviewed; 1437 AA.
AC P03369;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 228.
DE RecName: Full=Gag-Pol polyprotein;
DE AltName: Full=Pr160Gag-Pol;
DE Contains:
DE RecName: Full=Matrix protein p17;
DE Short=MA;
DE Contains:
DE RecName: Full=Capsid protein p24;
DE Short=CA;
DE Contains:
DE RecName: Full=Spacer peptide 1 {ECO:0000250|UniProtKB:P12497};
DE Short=SP1;
DE AltName: Full=p2;
DE Contains:
DE RecName: Full=Nucleocapsid protein p7;
DE Short=NC;
DE Contains:
DE RecName: Full=Transframe peptide;
DE Short=TF;
DE Contains:
DE RecName: Full=p6-pol;
DE Short=p6*;
DE Contains:
DE RecName: Full=Protease;
DE EC=3.4.23.16;
DE AltName: Full=PR;
DE AltName: Full=Retropepsin;
DE Contains:
DE RecName: Full=Reverse transcriptase/ribonuclease H;
DE EC=2.7.7.49;
DE EC=2.7.7.7;
DE EC=3.1.26.13;
DE AltName: Full=Exoribonuclease H;
DE EC=3.1.13.2;
DE AltName: Full=p66 RT;
DE Contains:
DE RecName: Full=p51 RT;
DE Contains:
DE RecName: Full=p15;
DE Contains:
DE RecName: Full=Integrase;
DE Short=IN;
DE EC=2.7.7.- {ECO:0000250|UniProtKB:P04585};
DE EC=3.1.-.- {ECO:0000250|UniProtKB:P04585};
GN Name=gag-pol;
OS Human immunodeficiency virus type 1 group M subtype B (isolate ARV2/SF2)
OS (HIV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11685;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=2578227; DOI=10.1126/science.2578227;
RA Sanchez-Pescador R., Power M.D., Barr P.J., Steimer K.S., Stempien M.M.,
RA Brown-Shimer S.L., Gee W.W., Renard A., Randolph A., Levy J.A., Dina D.,
RA Luciw P.A.;
RT "Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-
RT 2).";
RL Science 227:484-492(1985).
RN [2]
RP RIBOSOMAL FRAMESHIFT.
RX PubMed=2447506; DOI=10.1038/331280a0;
RA Jacks T., Power M.D., Masiarz F.R., Luciw P.A., Barr P.J., Varmus H.E.;
RT "Characterization of ribosomal frameshifting in HIV-1 gag-pol expression.";
RL Nature 331:280-283(1988).
RN [3]
RP REVIEW.
RX PubMed=8791726; DOI=10.1007/978-3-642-80145-7_4;
RA Vogt V.M.;
RT "Proteolytic processing and particle maturation.";
RL Curr. Top. Microbiol. Immunol. 214:95-131(1996).
RN [4]
RP REVIEW.
RX PubMed=9878383; DOI=10.1006/jmbi.1998.2354;
RA Turner B.G., Summers M.F.;
RT "Structural biology of HIV.";
RL J. Mol. Biol. 285:1-32(1999).
RN [5]
RP REVIEW.
RX PubMed=11700285; DOI=10.1146/annurev.genet.35.102401.090551;
RA Negroni M., Buc H.;
RT "Mechanisms of retroviral recombination.";
RL Annu. Rev. Genet. 35:275-302(2001).
RN [6]
RP REVIEW.
RX PubMed=11983066; DOI=10.1186/gb-2002-3-4-reviews3006;
RA Dunn B.M., Goodenow M.M., Gustchina A., Wlodawer A.;
RT "Retroviral proteases.";
RL Genome Biol. 3:REVIEWS3006.1-REVIEWS3006.7(2002).
RN [7]
RP REVIEW.
RX PubMed=12873766; DOI=10.1016/s0005-2736(03)00163-9;
RA Scarlata S., Carter C.;
RT "Role of HIV-1 Gag domains in viral assembly.";
RL Biochim. Biophys. Acta 1614:62-72(2003).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 491-589.
RX PubMed=2548279; DOI=10.1126/science.2548279;
RA Wlodawer A., Miller M., Jaskolski M., Sathyanarayana B.K., Baldwin E.,
RA Weber I.T., Selk L.M., Clawson L., Schneider J., Kent S.B.H.;
RT "Conserved folding in retroviral proteases: crystal structure of a
RT synthetic HIV-1 protease.";
RL Science 245:616-621(1989).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 491-589 IN COMPLEX WITH
RP HALOPERIDOL.
RX PubMed=8340363; DOI=10.1016/s0021-9258(18)82261-x;
RA Rutenber E.E., Fauman E.B., Keenan R.J., Fong S., Furth P.S.,
RA Ortiz de Montellano P.R., Meng E., Kuntz I.D., DeCamp D.L., Salto R.,
RA Rose J.R., Craik C.S., Stroud R.M.;
RT "Structure of a non-peptide inhibitor complexed with HIV-1 protease.
RT Developing a cycle of structure-based drug design.";
RL J. Biol. Chem. 268:15343-15346(1993).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 491-589 OF COMPLEX WITH INH.
RA Abbenante G., March D.R., Bergman D.A., Hunt P.A., Garnham B., Dancer R.J.,
RA Martin J.L., Fairlie D.P.;
RT "Regioselective structural and functional mimicry of peptides --design of
RT hydrolytically-stable cyclic peptidomimetic inhibitors of HIV-1 protease.";
RL J. Am. Chem. Soc. 117:10220-10226(1995).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 491-589 OF COMPLEX WITH INH.
RA March D.R., Abbenante G., Bergman D.A., Brinkworth R.I.,
RA Wickramasinghe W.A., Begun J., Martin J.L., Fairlie D.P.;
RT "Substrate-based cyclic peptidomimetics of Phe-Ile-Val that inhibit HIV-1
RT protease using a novel enzyme-binding mode.";
RL J. Am. Chem. Soc. 118:3375-3379(1996).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 491-589.
RX PubMed=8841139; DOI=10.1021/bi9612733;
RA Rose R.B., Craik C.S., Douglas N.L., Stroud R.M.;
RT "Three-dimensional structures of HIV-1 and SIV protease product
RT complexes.";
RL Biochemistry 35:12933-12944(1996).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 491-589.
RX PubMed=8894111; DOI=10.1016/0968-0896(96)00147-2;
RA Rutenber E.E., McPhee F., Kaplan A.P., Gallion S.L., Hogan J.C. Jr.,
RA Craik C.S., Stroud R.M.;
RT "A new class of HIV-1 protease inhibitor: the crystallographic structure,
RT inhibition and chemical synthesis of an aminimide peptide isostere.";
RL Bioorg. Med. Chem. 4:1545-1558(1996).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 491-589 IN COMPLEX WITH
RP MACROCYCLIC PEPTIDOMIMETIC INHIBITORS.
RX PubMed=10387041; DOI=10.1021/bi990174x;
RA Martin J.L., Begun J., Schindeler A., Wickramasinghe W.A., Alewood D.,
RA Alewood P.F., Bergman D.A., Brinkworth R.I., Abbenante G., March D.R.,
RA Reid R.C., Fairlie D.P.;
RT "Molecular recognition of macrocyclic peptidomimetic inhibitors by HIV-1
RT protease.";
RL Biochemistry 38:7978-7988(1999).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.09 ANGSTROMS) OF 491-589 IN COMPLEX WITH THE
RP INHIBITOR JE-2147.
RX PubMed=10346931; DOI=10.1021/jm980637h;
RA Mimoto T., Kato R., Takaku H., Nojima S., Terashima K., Misawa S.,
RA Fukazawa T., Ueno T., Sato H., Shintani M., Kiso Y., Hayashi H.;
RT "Structure-activity relationship of small-sized HIV protease inhibitors
RT containing allophenylnorstatine.";
RL J. Med. Chem. 42:1789-1802(1999).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 491-589 IN COMPLEX WITH
RP MACROCYCLIC PEPTIDOMIMETIC INHIBITORS.
RX PubMed=11000004; DOI=10.1021/jm000013n;
RA Tyndall J.D., Reid R.C., Tyssen D.P., Jardine D.K., Todd B., Passmore M.,
RA March D.R., Pattenden L.K., Bergman D.A., Alewood D., Hu S.H.,
RA Alewood P.F., Birch C.J., Martin J.L., Fairlie D.P.;
RT "Synthesis, stability, antiviral activity, and protease-bound structures of
RT substrate-mimicking constrained macrocyclic inhibitors of HIV-1 protease.";
RL J. Med. Chem. 43:3495-3504(2000).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 491-589 IN COMPLEX WITH SUBSTRATE.
RX PubMed=10966816; DOI=10.1006/jmbi.2000.4018;
RA Prabu-Jeyabalan M., Nalivaika E.A., Schiffer C.A.;
RT "How does a symmetric dimer recognize an asymmetric substrate? A substrate
RT complex of HIV-1 protease.";
RL J. Mol. Biol. 301:1207-1220(2000).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 491-589 IN COMPLEX WITH
RP SUBSTRATES.
RX PubMed=12005435; DOI=10.1016/s0969-2126(02)00720-7;
RA Prabu-Jeyabalan M., Nalivaika E.A., Schiffer C.A.;
RT "Substrate shape determines specificity of recognition for HIV-1 protease:
RT analysis of crystal structures of six substrate complexes.";
RL Structure 10:369-381(2002).
CC -!- FUNCTION: [Gag-Pol polyprotein]: Mediates, with Gag polyprotein, the
CC essential events in virion assembly, including binding the plasma
CC membrane, making the protein-protein interactions necessary to create
CC spherical particles, recruiting the viral Env proteins, and packaging
CC the genomic RNA via direct interactions with the RNA packaging sequence
CC (Psi). Gag-Pol polyprotein may regulate its own translation, by the
CC binding genomic RNA in the 5'-UTR. At low concentration, the
CC polyprotein would promote translation, whereas at high concentration,
CC the polyprotein would encapsidate genomic RNA and then shut off
CC translation. {ECO:0000250}.
CC -!- FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma
CC membrane via a multipartite membrane-binding signal, that includes its
CC myristoylated N-terminus. Matrix protein is part of the pre-integration
CC complex. Implicated in the release from host cell mediated by Vpu.
CC Binds to RNA. {ECO:0000250|UniProtKB:P12497}.
CC -!- FUNCTION: [Capsid protein p24]: Forms the conical core that
CC encapsulates the genomic RNA-nucleocapsid complex in the virion. Most
CC core are conical, with only 7% tubular. The core is constituted by
CC capsid protein hexamer subunits. The core is disassembled soon after
CC virion entry (By similarity). Host restriction factors such as TRIM5-
CC alpha or TRIMCyp bind retroviral capsids and cause premature capsid
CC disassembly, leading to blocks in reverse transcription. Capsid
CC restriction by TRIM5 is one of the factors which restricts HIV-1 to the
CC human species. Host PIN1 apparently facilitates the virion uncoating.
CC On the other hand, interactions with PDZD8 or CYPA stabilize the
CC capsid. {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.
CC -!- FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral
CC dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc
CC fingers. Acts as a nucleic acid chaperone which is involved in
CC rearangement of nucleic acid secondary structure during gRNA
CC retrotranscription. Also facilitates template switch leading to
CC recombination. As part of the polyprotein, participates in gRNA
CC dimerization, packaging, tRNA incorporation and virion assembly.
CC {ECO:0000250|UniProtKB:P04585}.
CC -!- FUNCTION: [Protease]: Aspartyl protease that mediates proteolytic
CC cleavages of Gag and Gag-Pol polyproteins during or shortly after the
CC release of the virion from the plasma membrane. Cleavages take place as
CC an ordered, step-wise cascade to yield mature proteins. This process is
CC called maturation. Displays maximal activity during the budding process
CC just prior to particle release from the cell. Also cleaves Nef and Vif,
CC probably concomitantly with viral structural proteins on maturation of
CC virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off
CC the capped cellular mRNA translation. The resulting inhibition of
CC cellular protein synthesis serves to ensure maximal viral gene
CC expression and to evade host immune response. Also mediates cleavage of
CC host YTHDF3. Mediates cleavage of host CARD8, thereby activating the
CC CARD8 inflammasome, leading to the clearance of latent HIV-1 in patient
CC CD4(+) T-cells after viral reactivation; in contrast, HIV-1 can evade
CC CARD8-sensing when its protease remains inactive in infected cells
CC prior to viral budding (By similarity). {ECO:0000250|UniProtKB:P04585,
CC ECO:0000255|PROSITE-ProRule:PRU00275}.
CC -!- FUNCTION: [Reverse transcriptase/ribonuclease H]: Multifunctional
CC enzyme that converts the viral RNA genome into dsDNA in the cytoplasm,
CC shortly after virus entry into the cell. This enzyme displays a DNA
CC polymerase activity that can copy either DNA or RNA templates, and a
CC ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-
CC DNA heteroduplexes in a partially processive 3' to 5' endonucleasic
CC mode. Conversion of viral genomic RNA into dsDNA requires many steps. A
CC tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-
CC end of the viral RNA. RT uses the 3' end of the tRNA primer to perform
CC a short round of RNA-dependent minus-strand DNA synthesis. The reading
CC proceeds through the U5 region and ends after the repeated (R) region
CC which is present at both ends of viral RNA. The portion of the RNA-DNA
CC heteroduplex is digested by the RNase H, resulting in a ssDNA product
CC attached to the tRNA primer. This ssDNA/tRNA hybridizes with the
CC identical R region situated at the 3' end of viral RNA. This template
CC exchange, known as minus-strand DNA strong stop transfer, can be either
CC intra- or intermolecular. RT uses the 3' end of this newly synthesized
CC short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of
CC the whole template. RNase H digests the RNA template except for two
CC polypurine tracts (PPTs) situated at the 5'-end and near the center of
CC the genome. It is not clear if both polymerase and RNase H activities
CC are simultaneous. RNase H probably can proceed both in a polymerase-
CC dependent (RNA cut into small fragments by the same RT performing DNA
CC synthesis) and a polymerase-independent mode (cleavage of remaining RNA
CC fragments by free RTs). Secondly, RT performs DNA-directed plus-strand
CC DNA synthesis using the PPTs that have not been removed by RNase H as
CC primers. PPTs and tRNA primers are then removed by RNase H. The 3' and
CC 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate.
CC Strand displacement synthesis by RT to the PBS and PPT ends produces a
CC blunt ended, linear dsDNA copy of the viral genome that includes long
CC terminal repeats (LTRs) at both ends. {ECO:0000250|UniProtKB:P04585}.
CC -!- FUNCTION: [Integrase]: Catalyzes viral DNA integration into the host
CC chromosome, by performing a series of DNA cutting and joining
CC reactions. This enzyme activity takes place after virion entry into a
CC cell and reverse transcription of the RNA genome in dsDNA. The first
CC step in the integration process is 3' processing. This step requires a
CC complex comprising the viral genome, matrix protein, Vpr and integrase.
CC This complex is called the pre-integration complex (PIC). The integrase
CC protein removes 2 nucleotides from each 3' end of the viral DNA,
CC leaving recessed CA OH's at the 3' ends. In the second step, the PIC
CC enters cell nucleus. This process is mediated through integrase and Vpr
CC proteins, and allows the virus to infect a non dividing cell. This
CC ability to enter the nucleus is specific of lentiviruses, other
CC retroviruses cannot and rely on cell division to access cell
CC chromosomes. In the third step, termed strand transfer, the integrase
CC protein joins the previously processed 3' ends to the 5' ends of
CC strands of target cellular DNA at the site of integration. The 5'-ends
CC are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-
CC shaped, gapped, recombination intermediate results, with the 5'-ends of
CC the viral DNA strands and the 3' ends of target DNA strands remaining
CC unjoined, flanking a gap of 5 bp. The last step is viral DNA
CC integration into host chromosome. This involves host DNA repair
CC synthesis in which the 5 bp gaps between the unjoined strands are
CC filled in and then ligated. Since this process occurs at both cuts
CC flanking the HIV genome, a 5 bp duplication of host DNA is produced at
CC the ends of HIV-1 integration. Alternatively, Integrase may catalyze
CC the excision of viral DNA just after strand transfer, this is termed
CC disintegration. {ECO:0000250|UniProtKB:P04585}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Specific for a P1 residue that is hydrophobic, and P1'
CC variable, but often Pro.; EC=3.4.23.16;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00275};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endohydrolysis of RNA in RNA/DNA hybrids. Three different
CC cleavage modes: 1. sequence-specific internal cleavage of RNA. Human
CC immunodeficiency virus type 1 and Moloney murine leukemia virus
CC enzymes prefer to cleave the RNA strand one nucleotide away from the
CC RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides
CC from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides
CC away from the primer terminus.; EC=3.1.26.13; Evidence={ECO:0000250};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3'-end directed exonucleolytic cleavage of viral RNA-DNA
CC hybrid.; EC=3.1.13.2; Evidence={ECO:0000250};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) =
CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339,
CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560,
CC ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00405};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) =
CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339,
CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560,
CC ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00405};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Binds 2 magnesium ions for reverse transcriptase polymerase
CC activity. {ECO:0000250};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity.
CC Substrate-binding is a precondition for magnesium binding.
CC {ECO:0000250};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Magnesium ions are required for integrase activity. Binds at least
CC 1, maybe 2 magnesium ions. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Protease: The viral protease is inhibited by many
CC synthetic protease inhibitors (PIs), such as amprenavir, atazanavir,
CC indinavir, loprinavir, nelfinavir, ritonavir and saquinavir. Use of
CC protease inhibitors in tritherapy regimens permit more ambitious
CC therapeutic strategies. Reverse transcriptase/ribonuclease H: RT can be
CC inhibited either by nucleoside RT inhibitors (NRTIs) or by non
CC nucleoside RT inhibitors (NNRTIs). NRTIs act as chain terminators,
CC whereas NNRTIs inhibit DNA polymerization by binding a small
CC hydrophobic pocket near the RT active site and inducing an allosteric
CC change in this region. Classical NRTIs are abacavir, adefovir (PMEA),
CC didanosine (ddI), lamivudine (3TC), stavudine (d4T), tenofovir (PMPA),
CC zalcitabine (ddC), and zidovudine (AZT). Classical NNRTIs are
CC atevirdine (BHAP U-87201E), delavirdine, efavirenz (DMP-266), emivirine
CC (I-EBU), and nevirapine (BI-RG-587). The tritherapies used as a basic
CC effective treatment of AIDS associate two NRTIs and one NNRTI.
CC {ECO:0000250}.
CC -!- SUBUNIT: [Matrix protein p17]: Homotrimer; further assembles as
CC hexamers of trimers (By similarity). Interacts with gp41 (via C-
CC terminus) (By similarity). Interacts with host CALM1; this interaction
CC induces a conformational change in the Matrix protein, triggering
CC exposure of the myristate group (By similarity). Interacts with host
CC AP3D1; this interaction allows the polyprotein trafficking to
CC multivesicular bodies during virus assembly (By similarity). Part of
CC the pre-integration complex (PIC) which is composed of viral genome,
CC matrix protein, Vpr and integrase (By similarity).
CC {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.
CC -!- SUBUNIT: [Capsid protein p24]: Homodimer; the homodimer further
CC multimerizes as homohexamers or homopentamers. Interacts with human
CC PPIA/CYPA (By similarity); This interaction stabilizes the capsid.
CC Interacts with human NUP153 (By similarity). Interacts with host PDZD8;
CC this interaction stabilizes the capsid (By similarity). Interacts with
CC monkey TRIM5; this interaction destabilizes the capsid (By similarity).
CC {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.
CC -!- SUBUNIT: [Protease]: Homodimer, whose active site consists of two
CC apposed aspartic acid residues. {ECO:0000250|UniProtKB:P04585,
CC ECO:0000250|UniProtKB:P12497}.
CC -!- SUBUNIT: [Reverse transcriptase/ribonuclease H]: Heterodimer of p66 RT
CC and p51 RT (RT p66/p51) (By similarity). Heterodimerization of RT is
CC essential for DNA polymerase activity (By similarity). The overall
CC folding of the subdomains is similar in p66 RT and p51 RT but the
CC spatial arrangements of the subdomains are dramatically different (By
CC similarity). {ECO:0000250|UniProtKB:P03366}.
CC -!- SUBUNIT: [Integrase]: Homotetramer; may further associate as a
CC homohexadecamer (By similarity). Part of the pre-integration complex
CC (PIC) which is composed of viral genome, matrix protein, Vpr and
CC integrase. Interacts with human SMARCB1/INI1 and human PSIP1/LEDGF
CC isoform 1. Interacts with human KPNA3; this interaction might play a
CC role in nuclear import of the pre-integration complex (By similarity).
CC Interacts with human NUP153; this interaction might play a role in
CC nuclear import of the pre-integration complex (By similarity).
CC {ECO:0000250|UniProtKB:P03367, ECO:0000250|UniProtKB:P04585,
CC ECO:0000250|UniProtKB:P12497}.
CC -!- SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane; Lipid-
CC anchor. Host endosome, host multivesicular body. Note=These locations
CC are linked to virus assembly sites. The main location is the cell
CC membrane, but under some circumstances, late endosomal compartments can
CC serve as productive sites for virion assembly.
CC {ECO:0000250|UniProtKB:P12497}.
CC -!- SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane; Lipid-
CC anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Reverse transcriptase/ribonuclease H]: Virion
CC {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Integrase]: Virion {ECO:0000305}. Host nucleus
CC {ECO:0000305}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial
CC phase, cytoplasmic at assembly. {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=2;
CC Comment=Translation results in the formation of the Gag polyprotein
CC most of the time. Ribosomal frameshifting at the gag-pol genes
CC boundary occurs at low frequency and produces the Gag-Pol
CC polyprotein. This strategy of translation probably allows the virus
CC to modulate the quantity of each viral protein. Maintenance of a
CC correct Gag to Gag-Pol ratio is essential for RNA dimerization and
CC viral infectivity. {ECO:0000269|PubMed:2447506};
CC Name=Gag-Pol polyprotein;
CC IsoId=P03369-1; Sequence=Displayed;
CC Name=Gag polyprotein;
CC IsoId=P03349-1; Sequence=External;
CC -!- DOMAIN: [Reverse transcriptase/ribonuclease H]: RT is structured in
CC five subdomains: finger, palm, thumb, connection and RNase H. Within
CC the palm subdomain, the 'primer grip' region is thought to be involved
CC in the positioning of the primer terminus for accommodating the
CC incoming nucleotide. The RNase H domain stabilizes the association of
CC RT with primer-template. {ECO:0000250}.
CC -!- DOMAIN: [Reverse transcriptase/ribonuclease H]: The tryptophan repeat
CC motif is involved in RT p66/p51 dimerization (By similarity).
CC {ECO:0000250}.
CC -!- DOMAIN: [Integrase]: The core domain contains the D-x(n)-D-x(35)-E
CC motif, named for the phylogenetically conserved glutamic acid and
CC aspartic acid residues and the invariant 35 amino acid spacing between
CC the second and third acidic residues. Each acidic residue of the
CC D,D(35)E motif is independently essential for the 3'-processing and
CC strand transfer activities of purified integrase protein.
CC {ECO:0000250}.
CC -!- PTM: [Gag-Pol polyprotein]: Specific enzymatic cleavages by the viral
CC protease yield mature proteins. The protease is released by
CC autocatalytic cleavage. The polyprotein is cleaved during and after
CC budding, this process is termed maturation. Proteolytic cleavage of p66
CC RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid
CC protein p7 might be further cleaved after virus entry.
CC {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00405}.
CC -!- PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the
CC virion by a host kinase. Phosphorylation is apparently not a major
CC regulator of membrane association. {ECO:0000250|UniProtKB:P04585}.
CC -!- PTM: [Capsid protein p24]: Phosphorylated possibly by host MAPK1; this
CC phosphorylation is necessary for Pin1-mediated virion uncoating.
CC {ECO:0000250|UniProtKB:P12493}.
CC -!- PTM: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its
CC function by reducing RNA annealing and the initiation of reverse
CC transcription. {ECO:0000250|UniProtKB:P03347}.
CC -!- MISCELLANEOUS: [Reverse transcriptase/ribonuclease H]: Error-prone
CC enzyme that lacks a proof-reading function. High mutations rate is a
CC direct consequence of this characteristic. RT also displays frequent
CC template switching leading to high recombination rate. Recombination
CC mostly occurs between homologous regions of the two copackaged RNA
CC genomes. If these two RNA molecules derive from different viral
CC strains, reverse transcription will give rise to highly recombinated
CC proviral DNAs. {ECO:0000250}.
CC -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC majority of strains found worldwide belong to the group M. Group O
CC seems to be endemic to and largely confined to Cameroon and neighboring
CC countries in West Central Africa, where these viruses represent a small
CC minority of HIV-1 strains. The group N is represented by a limited
CC number of isolates from Cameroonian persons. The group M is further
CC subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC -!- MISCELLANEOUS: Resistance to inhibitors associated with mutations are
CC observed both in viral protease and in reverse transcriptase. Most of
CC the time, single mutations confer only a modest reduction in drug
CC susceptibility. Combination of several mutations is usually required to
CC develop a high-level drug resistance. These mutations are predominantly
CC found in clade B viruses and not in other genotypes. They are listed in
CC the clade B representative isolate HXB2 (AC P04585).
CC -!- MISCELLANEOUS: [Isoform Gag-Pol polyprotein]: Produced by -1 ribosomal
CC frameshifting.
CC -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
CC -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC URL="https://hivdb.stanford.edu";
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DR EMBL; K02007; AAB59876.1; ALT_SEQ; Genomic_RNA.
DR PIR; A03968; GNVWA2.
DR PDB; 1AID; X-ray; 2.20 A; A/B=491-589.
DR PDB; 1B6J; X-ray; 1.85 A; A/B=491-589.
DR PDB; 1B6K; X-ray; 1.85 A; A/B=491-589.
DR PDB; 1B6L; X-ray; 1.75 A; A/B=491-589.
DR PDB; 1B6M; X-ray; 1.85 A; A/B=491-589.
DR PDB; 1B6P; X-ray; 2.00 A; A/B=491-589.
DR PDB; 1CPI; X-ray; 2.05 A; A/B=491-589.
DR PDB; 1D4K; X-ray; 1.85 A; A/B=491-589.
DR PDB; 1D4L; X-ray; 1.75 A; A/B=491-589.
DR PDB; 1F7A; X-ray; 2.00 A; A/B=491-589.
DR PDB; 1KJ4; X-ray; 2.90 A; A/B/C/D=491-589.
DR PDB; 1KJ7; X-ray; 2.00 A; A/B=491-589.
DR PDB; 1KJF; X-ray; 2.00 A; A/B=491-589.
DR PDB; 1KJG; X-ray; 2.00 A; A/B=491-589, P=1025-1034.
DR PDB; 1KJH; X-ray; 2.00 A; A/B=491-589.
DR PDB; 1KZK; X-ray; 1.09 A; A/B=491-589.
DR PDB; 1MT7; X-ray; 1.90 A; A/B=491-589.
DR PDB; 1MT8; X-ray; 2.15 A; A/B=491-589.
DR PDB; 1MT9; X-ray; 2.00 A; A/B=491-589.
DR PDB; 1MTB; X-ray; 2.50 A; A/B=491-589.
DR PDB; 1MTR; X-ray; 1.75 A; A/B=491-589.
DR PDB; 1N49; X-ray; 2.20 A; A/B/C/D=491-589.
DR PDB; 1T3R; X-ray; 1.20 A; A/B=491-589.
DR PDB; 1TSQ; X-ray; 2.00 A; A/B=491-589.
DR PDB; 1TSU; X-ray; 2.10 A; A/B=491-589.
DR PDB; 1YTG; X-ray; 2.30 A; A/B=491-589.
DR PDB; 1YTH; X-ray; 2.20 A; A/B=491-589.
DR PDB; 1Z1H; X-ray; 1.85 A; A/B=491-589.
DR PDB; 1Z1R; X-ray; 1.85 A; A/B=491-589.
DR PDB; 2AID; X-ray; 1.90 A; A/B=491-589.
DR PDB; 2F3K; X-ray; 1.60 A; A/B=491-588.
DR PDB; 2FGU; X-ray; 2.00 A; A/B=491-589.
DR PDB; 2FGV; X-ray; 1.50 A; A/B=491-589.
DR PDB; 2FNS; X-ray; 1.85 A; A/B=491-589.
DR PDB; 2FNT; X-ray; 1.44 A; A/B=491-589.
DR PDB; 2J9J; X-ray; 1.04 A; A/B=491-589.
DR PDB; 2J9K; X-ray; 1.20 A; A/B=491-589.
DR PDB; 2JE4; X-ray; 1.07 A; A/B=491-589.
DR PDB; 2NXD; X-ray; 2.00 A; A/B=491-589.
DR PDB; 2NXL; X-ray; 2.00 A; A/B=491-589.
DR PDB; 2NXM; X-ray; 2.25 A; A/B=491-589.
DR PDB; 2Q3K; X-ray; 2.00 A; A/B=491-589.
DR PDB; 2QHY; X-ray; 1.85 A; A/B=491-589.
DR PDB; 2QHZ; X-ray; 1.85 A; A/B=491-589.
DR PDB; 2QI0; X-ray; 2.10 A; A/B=491-589.
DR PDB; 2QI1; X-ray; 2.00 A; A/B=491-589.
DR PDB; 2QI3; X-ray; 1.95 A; A/B=491-589.
DR PDB; 2QI4; X-ray; 1.80 A; A/B=491-589.
DR PDB; 2QI5; X-ray; 1.85 A; A/B=491-589.
DR PDB; 2QI6; X-ray; 1.85 A; A/B=491-589.
DR PDB; 2QI7; X-ray; 1.85 A; A/B=491-589.
DR PDB; 3AID; X-ray; 2.50 A; A/B=491-589.
DR PDB; 3BXR; X-ray; 1.60 A; A/B=491-589.
DR PDB; 3BXS; X-ray; 1.60 A; A/B=491-589.
DR PDB; 3EKP; X-ray; 2.15 A; A/B/C/D=491-589.
DR PDB; 3EKQ; X-ray; 2.20 A; A/B=491-589.
DR PDB; 3EKT; X-ray; 1.97 A; A/B/C/D=491-589.
DR PDB; 3EKV; X-ray; 1.75 A; A/B=491-589.
DR PDB; 3EKW; X-ray; 1.60 A; A/B=491-589.
DR PDB; 3EKX; X-ray; 1.97 A; A/B=491-589.
DR PDB; 3EKY; X-ray; 1.80 A; A/B=491-589.
DR PDB; 3EL0; X-ray; 2.00 A; A/B=491-589.
DR PDB; 3EL1; X-ray; 1.70 A; A/B=491-589.
DR PDB; 3EL4; X-ray; 2.00 A; A/B=491-589.
DR PDB; 3EL5; X-ray; 1.60 A; A/B=491-589.
DR PDB; 3EL9; X-ray; 1.60 A; A/B=491-589.
DR PDB; 3EM3; X-ray; 2.20 A; A/B=491-589.
DR PDB; 3EM4; X-ray; 2.10 A; A/B/U/V=491-589.
DR PDB; 3EM6; X-ray; 2.10 A; A/B=491-589.
DR PDB; 3FSM; X-ray; 1.60 A; A=491-589.
DR PDB; 3GI0; X-ray; 1.80 A; A/B=491-589.
DR PDB; 3GI4; X-ray; 1.85 A; A/B=491-589.
DR PDB; 3GI5; X-ray; 1.80 A; A/B=491-589.
DR PDB; 3GI6; X-ray; 1.84 A; A/B=491-589.
DR PDB; 3HAU; X-ray; 1.30 A; A/B=491-589.
DR PDB; 3HAW; X-ray; 1.30 A; A/B=491-589.
DR PDB; 3HBO; X-ray; 1.71 A; A/B=491-589.
DR PDB; 3HDK; X-ray; 1.80 A; A/B=491-589.
DR PDB; 3HLO; X-ray; 1.60 A; A=491-589.
DR PDB; 3HVP; X-ray; 2.80 A; A=491-589.
DR PDB; 3HZC; X-ray; 1.45 A; A=491-589.
DR PDB; 3I2L; X-ray; 1.50 A; A/B=491-589.
DR PDB; 3I7E; X-ray; 1.70 A; A/B=491-589.
DR PDB; 3IAW; X-ray; 1.61 A; A=491-589.
DR PDB; 3KA2; X-ray; 1.40 A; A=491-589.
DR PDB; 3LZV; X-ray; 2.15 A; A/B=491-589.
DR PDB; 3MXD; X-ray; 1.95 A; A/B=491-589.
DR PDB; 3MXE; X-ray; 1.85 A; A/B=491-589.
DR PDB; 3NWQ; X-ray; 1.50 A; A/B=491-589.
DR PDB; 3NWX; X-ray; 1.90 A; A/B=491-589.
DR PDB; 3NXN; X-ray; 1.80 A; A=491-589.
DR PDB; 3NYG; X-ray; 1.45 A; A/B=491-589.
DR PDB; 3O9F; X-ray; 1.70 A; A/B=491-589.
DR PDB; 3O9G; X-ray; 1.65 A; A/B=491-589.
DR PDB; 3O9H; X-ray; 1.70 A; A/B=491-589.
DR PDB; 3O9I; X-ray; 1.45 A; A/B=491-589.
DR PDB; 3OXV; X-ray; 1.75 A; A/B/C/D=491-589.
DR PDB; 3OXW; X-ray; 1.95 A; A/B/C/D=491-589.
DR PDB; 3OXX; X-ray; 1.65 A; A/B/C/D=491-589.
DR PDB; 3OY4; X-ray; 1.76 A; A/B=491-589.
DR PDB; 3R4B; X-ray; 1.90 A; A/B=491-589.
DR PDB; 4EP2; X-ray; 1.90 A; A=486-589.
DR PDB; 4EP3; X-ray; 1.81 A; A=486-589.
DR PDB; 4EPJ; X-ray; 1.69 A; A=486-589.
DR PDB; 4EQ0; X-ray; 1.70 A; A=486-589.
DR PDB; 4EQJ; X-ray; 1.80 A; A=486-589.
DR PDB; 4F73; X-ray; 1.90 A; A/B=491-589.
DR PDB; 4F74; X-ray; 2.20 A; A/B=491-589.
DR PDB; 4F75; X-ray; 1.70 A; A/B=491-589.
DR PDB; 4F76; X-ray; 1.85 A; A/B=491-589.
DR PDB; 4HVP; X-ray; 2.30 A; A/B=491-589.
DR PDB; 4OBD; X-ray; 1.90 A; A/B/C/D=491-589.
DR PDB; 4OBF; X-ray; 1.68 A; A/B/C/D=491-589.
DR PDB; 4OBG; X-ray; 1.78 A; A/B/C/D=491-589.
DR PDB; 4OBH; X-ray; 1.85 A; A/B/C/D=491-589.
DR PDB; 4OBJ; X-ray; 1.75 A; A/B=491-589.
DR PDB; 4OBK; X-ray; 1.65 A; A/B=491-589.
DR PDB; 4QJ2; X-ray; 2.13 A; A/B/C/D=491-589.
DR PDB; 4QJ6; X-ray; 1.50 A; A/B/C/D=491-589.
DR PDB; 4QJ7; X-ray; 1.67 A; A/B/C/D=491-589.
DR PDB; 4QJ8; X-ray; 2.00 A; A/B/C/D=491-589.
DR PDB; 4QJ9; X-ray; 1.83 A; A/B=491-589.
DR PDB; 4QJA; X-ray; 1.54 A; A/B=491-589.
DR PDB; 7HVP; X-ray; 2.40 A; A/B=491-589.
DR PDB; 8HVP; X-ray; 2.50 A; A/B=491-589.
DR PDBsum; 1AID; -.
DR PDBsum; 1B6J; -.
DR PDBsum; 1B6K; -.
DR PDBsum; 1B6L; -.
DR PDBsum; 1B6M; -.
DR PDBsum; 1B6P; -.
DR PDBsum; 1CPI; -.
DR PDBsum; 1D4K; -.
DR PDBsum; 1D4L; -.
DR PDBsum; 1F7A; -.
DR PDBsum; 1KJ4; -.
DR PDBsum; 1KJ7; -.
DR PDBsum; 1KJF; -.
DR PDBsum; 1KJG; -.
DR PDBsum; 1KJH; -.
DR PDBsum; 1KZK; -.
DR PDBsum; 1MT7; -.
DR PDBsum; 1MT8; -.
DR PDBsum; 1MT9; -.
DR PDBsum; 1MTB; -.
DR PDBsum; 1MTR; -.
DR PDBsum; 1N49; -.
DR PDBsum; 1T3R; -.
DR PDBsum; 1TSQ; -.
DR PDBsum; 1TSU; -.
DR PDBsum; 1YTG; -.
DR PDBsum; 1YTH; -.
DR PDBsum; 1Z1H; -.
DR PDBsum; 1Z1R; -.
DR PDBsum; 2AID; -.
DR PDBsum; 2F3K; -.
DR PDBsum; 2FGU; -.
DR PDBsum; 2FGV; -.
DR PDBsum; 2FNS; -.
DR PDBsum; 2FNT; -.
DR PDBsum; 2J9J; -.
DR PDBsum; 2J9K; -.
DR PDBsum; 2JE4; -.
DR PDBsum; 2NXD; -.
DR PDBsum; 2NXL; -.
DR PDBsum; 2NXM; -.
DR PDBsum; 2Q3K; -.
DR PDBsum; 2QHY; -.
DR PDBsum; 2QHZ; -.
DR PDBsum; 2QI0; -.
DR PDBsum; 2QI1; -.
DR PDBsum; 2QI3; -.
DR PDBsum; 2QI4; -.
DR PDBsum; 2QI5; -.
DR PDBsum; 2QI6; -.
DR PDBsum; 2QI7; -.
DR PDBsum; 3AID; -.
DR PDBsum; 3BXR; -.
DR PDBsum; 3BXS; -.
DR PDBsum; 3EKP; -.
DR PDBsum; 3EKQ; -.
DR PDBsum; 3EKT; -.
DR PDBsum; 3EKV; -.
DR PDBsum; 3EKW; -.
DR PDBsum; 3EKX; -.
DR PDBsum; 3EKY; -.
DR PDBsum; 3EL0; -.
DR PDBsum; 3EL1; -.
DR PDBsum; 3EL4; -.
DR PDBsum; 3EL5; -.
DR PDBsum; 3EL9; -.
DR PDBsum; 3EM3; -.
DR PDBsum; 3EM4; -.
DR PDBsum; 3EM6; -.
DR PDBsum; 3FSM; -.
DR PDBsum; 3GI0; -.
DR PDBsum; 3GI4; -.
DR PDBsum; 3GI5; -.
DR PDBsum; 3GI6; -.
DR PDBsum; 3HAU; -.
DR PDBsum; 3HAW; -.
DR PDBsum; 3HBO; -.
DR PDBsum; 3HDK; -.
DR PDBsum; 3HLO; -.
DR PDBsum; 3HVP; -.
DR PDBsum; 3HZC; -.
DR PDBsum; 3I2L; -.
DR PDBsum; 3I7E; -.
DR PDBsum; 3IAW; -.
DR PDBsum; 3KA2; -.
DR PDBsum; 3LZV; -.
DR PDBsum; 3MXD; -.
DR PDBsum; 3MXE; -.
DR PDBsum; 3NWQ; -.
DR PDBsum; 3NWX; -.
DR PDBsum; 3NXN; -.
DR PDBsum; 3NYG; -.
DR PDBsum; 3O9F; -.
DR PDBsum; 3O9G; -.
DR PDBsum; 3O9H; -.
DR PDBsum; 3O9I; -.
DR PDBsum; 3OXV; -.
DR PDBsum; 3OXW; -.
DR PDBsum; 3OXX; -.
DR PDBsum; 3OY4; -.
DR PDBsum; 3R4B; -.
DR PDBsum; 4EP2; -.
DR PDBsum; 4EP3; -.
DR PDBsum; 4EPJ; -.
DR PDBsum; 4EQ0; -.
DR PDBsum; 4EQJ; -.
DR PDBsum; 4F73; -.
DR PDBsum; 4F74; -.
DR PDBsum; 4F75; -.
DR PDBsum; 4F76; -.
DR PDBsum; 4HVP; -.
DR PDBsum; 4OBD; -.
DR PDBsum; 4OBF; -.
DR PDBsum; 4OBG; -.
DR PDBsum; 4OBH; -.
DR PDBsum; 4OBJ; -.
DR PDBsum; 4OBK; -.
DR PDBsum; 4QJ2; -.
DR PDBsum; 4QJ6; -.
DR PDBsum; 4QJ7; -.
DR PDBsum; 4QJ8; -.
DR PDBsum; 4QJ9; -.
DR PDBsum; 4QJA; -.
DR PDBsum; 7HVP; -.
DR PDBsum; 8HVP; -.
DR SMR; P03369; -.
DR BindingDB; P03369; -.
DR ChEMBL; CHEMBL3638331; -.
DR DrugBank; DB07910; (2S)-2-amino-3-phenylpropane-1,1-diol.
DR DrugBank; DB07679; (9S,12S)-9-(1-methylethyl)-7,10-dioxo-2-oxa-8,11-diazabicyclo[12.2.2]octadeca-1(16),14,17-triene-12-carboxylic acid.
DR DrugBank; DB02411; 2-(11-{2-[Benzenesulfonyl-(3-Methyl-Butyl)-Amino]-1-Hydroxy-Ethyl}-6,9-Dioxo-2-Oxa-7,10-Diaza-Bicyclo[11.2.2]Heptadeca-1(16),13(17),14-Trien-8-Yl)-Acetamide, Inhibitor 2.
DR DrugBank; DB08622; 4-(4-CHLORO-PHENYL)-1-{3-[2-(4-FLUORO-PHENYL)-[1,3]DITHIOLAN-2-YL]-PROPYL}-PIPERIDIN-4-OL.
DR DrugBank; DB04454; Alpha-Aminobutyric Acid.
DR DrugBank; DB04886; Calanolide A.
DR DrugBank; DB02668; JE-2147.
DR DrugBank; DB05644; KP-1461.
DR DrugBank; DB03768; N-[2-Hydroxy-2-(8-Isopropyl-6,9-Dioxo-2-Oxa-7,10-Diaza-Bicyclo[11.2.2]Heptadeca-1(16),13(17),14-Trien-11-Yl)-Ethyl]-N-(3-Methyl-Butyl)-Benzenesulfonamide,Inhibitor 3.
DR DrugBank; DB05228; RDEA806.
DR DrugCentral; P03369; -.
DR MEROPS; A02.001; -.
DR PRIDE; P03369; -.
DR EvolutionaryTrace; P03369; -.
DR PRO; PR:P03369; -.
DR Proteomes; UP000007688; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0072494; C:host multivesicular body; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0004533; F:exoribonuclease H activity; IEA:UniProtKB-EC.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003964; F:RNA-directed DNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0004523; F:RNA-DNA hybrid ribonuclease activity; IEA:InterPro.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0015074; P:DNA integration; IEA:UniProtKB-KW.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0075713; P:establishment of integrated proviral latency; IEA:UniProtKB-KW.
DR GO; GO:0039651; P:induction by virus of host cysteine-type endopeptidase activity involved in apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0044826; P:viral genome integration into host DNA; IEA:UniProtKB-KW.
DR GO; GO:0075732; P:viral penetration into host nucleus; IEA:UniProtKB-KW.
DR CDD; cd05482; HIV_retropepsin_like; 1.
DR Gene3D; 1.10.10.200; -; 1.
DR Gene3D; 1.10.1200.30; -; 1.
DR Gene3D; 1.10.150.90; -; 1.
DR Gene3D; 1.10.375.10; -; 1.
DR Gene3D; 2.30.30.10; -; 1.
DR Gene3D; 2.40.70.10; -; 1.
DR Gene3D; 3.30.420.10; -; 2.
DR Gene3D; 3.30.70.270; -; 3.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR045345; Gag_p24_C.
DR InterPro; IPR017856; Integrase-like_N.
DR InterPro; IPR036862; Integrase_C_dom_sf_retrovir.
DR InterPro; IPR001037; Integrase_C_retrovir.
DR InterPro; IPR001584; Integrase_cat-core.
DR InterPro; IPR003308; Integrase_Zn-bd_dom_N.
DR InterPro; IPR000071; Lentvrl_matrix_N.
DR InterPro; IPR012344; Matrix_HIV/RSV_N.
DR InterPro; IPR001995; Peptidase_A2_cat.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR InterPro; IPR034170; Retropepsin-like_cat_dom.
DR InterPro; IPR018061; Retropepsins.
DR InterPro; IPR008916; Retrov_capsid_C.
DR InterPro; IPR008919; Retrov_capsid_N.
DR InterPro; IPR010999; Retrovr_matrix.
DR InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR002156; RNaseH_domain.
DR InterPro; IPR036397; RNaseH_sf.
DR InterPro; IPR000477; RT_dom.
DR InterPro; IPR010659; RVT_connect.
DR InterPro; IPR010661; RVT_thumb.
DR InterPro; IPR001878; Znf_CCHC.
DR InterPro; IPR036875; Znf_CCHC_sf.
DR Pfam; PF00540; Gag_p17; 1.
DR Pfam; PF19317; Gag_p24_C; 1.
DR Pfam; PF00552; IN_DBD_C; 1.
DR Pfam; PF02022; Integrase_Zn; 1.
DR Pfam; PF00075; RNase_H; 1.
DR Pfam; PF00665; rve; 1.
DR Pfam; PF00077; RVP; 1.
DR Pfam; PF00078; RVT_1; 1.
DR Pfam; PF06815; RVT_connect; 1.
DR Pfam; PF06817; RVT_thumb; 1.
DR Pfam; PF00098; zf-CCHC; 2.
DR PRINTS; PR00234; HIV1MATRIX.
DR SMART; SM00343; ZnF_C2HC; 2.
DR SUPFAM; SSF46919; SSF46919; 1.
DR SUPFAM; SSF47836; SSF47836; 1.
DR SUPFAM; SSF47943; SSF47943; 1.
DR SUPFAM; SSF50122; SSF50122; 1.
DR SUPFAM; SSF50630; SSF50630; 1.
DR SUPFAM; SSF53098; SSF53098; 2.
DR SUPFAM; SSF56672; SSF56672; 1.
DR SUPFAM; SSF57756; SSF57756; 1.
DR PROSITE; PS50175; ASP_PROT_RETROV; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 1.
DR PROSITE; PS50994; INTEGRASE; 1.
DR PROSITE; PS51027; INTEGRASE_DBD; 1.
DR PROSITE; PS50879; RNASE_H_1; 1.
DR PROSITE; PS50878; RT_POL; 1.
DR PROSITE; PS50158; ZF_CCHC; 2.
DR PROSITE; PS50876; ZF_INTEGRASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activation of host caspases by virus; AIDS;
KW Aspartyl protease; Capsid protein; DNA integration; DNA recombination;
KW DNA-binding; DNA-directed DNA polymerase; Endonuclease;
KW Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host translation shutoff by virus; Host cell membrane;
KW Host cytoplasm; Host endosome; Host gene expression shutoff by virus;
KW Host membrane; Host nucleus; Host-virus interaction; Hydrolase;
KW Lipid-binding; Lipoprotein; Magnesium; Membrane; Metal-binding;
KW Modulation of host cell apoptosis by virus; Multifunctional enzyme;
KW Myristate; Nuclease; Nucleotidyltransferase; Phosphoprotein; Protease;
KW Reference proteome; Repeat; Ribosomal frameshifting; RNA-binding;
KW RNA-directed DNA polymerase; Transferase; Viral genome integration;
KW Viral nucleoprotein; Viral penetration into host nucleus;
KW Viral release from host cell; Virion; Virion maturation;
KW Virus entry into host cell; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed; by host"
FT /evidence="ECO:0000250"
FT CHAIN 2..1437
FT /note="Gag-Pol polyprotein"
FT /id="PRO_0000261260"
FT CHAIN 2..134
FT /note="Matrix protein p17"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042321"
FT CHAIN 135..365
FT /note="Capsid protein p24"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042322"
FT PEPTIDE 366..379
FT /note="Spacer peptide 1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042323"
FT CHAIN 380..434
FT /note="Nucleocapsid protein p7"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042324"
FT PEPTIDE 435..442
FT /note="Transframe peptide"
FT /evidence="ECO:0000255"
FT /id="PRO_0000246709"
FT CHAIN 443..490
FT /note="p6-pol"
FT /evidence="ECO:0000255"
FT /id="PRO_0000042325"
FT CHAIN 491..589
FT /note="Protease"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038651"
FT CHAIN 590..1149
FT /note="Reverse transcriptase/ribonuclease H"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042326"
FT CHAIN 590..1029
FT /note="p51 RT"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042327"
FT CHAIN 1030..1149
FT /note="p15"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042328"
FT CHAIN 1150..1437
FT /note="Integrase"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042329"
FT DOMAIN 510..579
FT /note="Peptidase A2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00275"
FT DOMAIN 633..823
FT /note="Reverse transcriptase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT DOMAIN 1023..1146
FT /note="RNase H type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT DOMAIN 1203..1353
FT /note="Integrase catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00457"
FT ZN_FING 392..409
FT /note="CCHC-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT ZN_FING 413..430
FT /note="CCHC-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT ZN_FING 1152..1193
FT /note="Integrase-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT DNA_BIND 1372..1419
FT /note="Integrase-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00506"
FT REGION 7..31
FT /note="Interaction with Gp41"
FT /evidence="ECO:0000250|UniProtKB:P12497"
FT REGION 8..43
FT /note="Interaction with host CALM1"
FT /evidence="ECO:0000250|UniProtKB:P04585"
FT REGION 12..19
FT /note="Interaction with host AP3D1"
FT /evidence="ECO:0000250|UniProtKB:P12497"
FT REGION 14..33
FT /note="Interaction with membrane phosphatidylinositol 4,5-
FT bisphosphate and RNA"
FT /evidence="ECO:0000250|UniProtKB:P12497"
FT REGION 73..77
FT /note="Interaction with membrane phosphatidylinositol 4,5-
FT bisphosphate"
FT /evidence="ECO:0000250|UniProtKB:P12497"
FT REGION 106..129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 191..229
FT /note="Interaction with human PPIA/CYPA and NUP153"
FT /evidence="ECO:0000250|UniProtKB:P12497"
FT REGION 279..365
FT /note="Dimerization/Multimerization of capsid protein p24"
FT /evidence="ECO:0000250|UniProtKB:P04585"
FT REGION 491..495
FT /note="Dimerization of protease"
FT /evidence="ECO:0000250|UniProtKB:P04585"
FT REGION 539..545
FT /note="Dimerization of protease"
FT /evidence="ECO:0000250|UniProtKB:P04585"
FT REGION 578..590
FT /note="Dimerization of protease"
FT /evidence="ECO:0000250|UniProtKB:P04585"
FT REGION 816..824
FT /note="RT 'primer grip'"
FT /evidence="ECO:0000250"
FT MOTIF 16..22
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT MOTIF 26..32
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 987..1003
FT /note="Tryptophan repeat motif"
FT /evidence="ECO:0000250"
FT ACT_SITE 515
FT /note="For protease activity; shared with dimeric partner"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT BINDING 699
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic; for reverse transcriptase
FT activity"
FT /evidence="ECO:0000250"
FT BINDING 774
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic; for reverse transcriptase
FT activity"
FT /evidence="ECO:0000250"
FT BINDING 775
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic; for reverse transcriptase
FT activity"
FT /evidence="ECO:0000250"
FT BINDING 1032
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic; for RNase H activity"
FT /evidence="ECO:0000250"
FT BINDING 1067
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic; for RNase H activity"
FT /evidence="ECO:0000250"
FT BINDING 1087
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic; for RNase H activity"
FT /evidence="ECO:0000250"
FT BINDING 1138
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic; for RNase H activity"
FT /evidence="ECO:0000250"
FT BINDING 1161
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT BINDING 1165
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT BINDING 1189
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT BINDING 1192
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT BINDING 1213
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /ligand_note="catalytic; for integrase activity"
FT /evidence="ECO:0000250"
FT BINDING 1265
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /ligand_note="catalytic; for integrase activity"
FT /evidence="ECO:0000250"
FT BINDING 1301
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /ligand_note="catalytic; for integrase activity"
FT /evidence="ECO:0000250|UniProtKB:P04585"
FT SITE 134..135
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 223..224
FT /note="Cis/trans isomerization of proline peptide bond; by
FT human PPIA/CYPA"
FT /evidence="ECO:0000250"
FT SITE 365..366
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 379..380
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 434..435
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000255"
FT SITE 442..443
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 490..491
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 589..590
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 990
FT /note="Essential for RT p66/p51 heterodimerization"
FT /evidence="ECO:0000250"
FT SITE 1003
FT /note="Essential for RT p66/p51 heterodimerization"
FT /evidence="ECO:0000250"
FT SITE 1029..1030
FT /note="Cleavage; by viral protease; partial"
FT /evidence="ECO:0000250"
FT SITE 1149..1150
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT MOD_RES 134
FT /note="Phosphotyrosine; by host"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-myristoyl glycine; by host"
FT /evidence="ECO:0000250"
FT TURN 476..479
FT /evidence="ECO:0007829|PDB:3KA2"
FT STRAND 485..487
FT /evidence="ECO:0007829|PDB:3KA2"
FT STRAND 492..494
FT /evidence="ECO:0007829|PDB:4HVP"
FT STRAND 495..497
FT /evidence="ECO:0007829|PDB:2J9J"
FT STRAND 500..505
FT /evidence="ECO:0007829|PDB:2J9J"
FT STRAND 508..514
FT /evidence="ECO:0007829|PDB:2J9J"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:2FNT"
FT STRAND 522..525
FT /evidence="ECO:0007829|PDB:2FNT"
FT STRAND 532..539
FT /evidence="ECO:0007829|PDB:2J9J"
FT STRAND 542..556
FT /evidence="ECO:0007829|PDB:2J9J"
FT STRAND 559..568
FT /evidence="ECO:0007829|PDB:2J9J"
FT STRAND 571..575
FT /evidence="ECO:0007829|PDB:2FGV"
FT HELIX 577..580
FT /evidence="ECO:0007829|PDB:2J9J"
FT TURN 581..584
FT /evidence="ECO:0007829|PDB:2J9J"
FT STRAND 586..588
FT /evidence="ECO:0007829|PDB:2J9J"
FT STRAND 599..601
FT /evidence="ECO:0007829|PDB:4EPJ"
FT STRAND 604..606
FT /evidence="ECO:0007829|PDB:3NXN"
FT STRAND 615..620
FT /evidence="ECO:0007829|PDB:3FSM"
SQ SEQUENCE 1437 AA; 162015 MW; FE17066A84A2B649 CRC64;
MGARASVLSG GELDKWEKIR LRPGGKKKYK LKHIVWASRE LERFAVNPGL LETSEGCRQI
LGQLQPSLQT GSEELRSLYN TVATLYCVHQ RIDVKDTKEA LEKIEEEQNK SKKKAQQAAA
AAGTGNSSQV SQNYPIVQNL QGQMVHQAIS PRTLNAWVKV VEEKAFSPEV IPMFSALSEG
ATPQDLNTML NTVGGHQAAM QMLKETINEE AAEWDRVHPV HAGPIAPGQM REPRGSDIAG
TTSTLQEQIG WMTNNPPIPV GEIYKRWIIL GLNKIVRMYS PTSILDIRQG PKEPFRDYVD
RFYKTLRAEQ ASQDVKNWMT ETLLVQNANP DCKTILKALG PAATLEEMMT ACQGVGGPGH
KARVLAEAMS QVTNPANIMM QRGNFRNQRK TVKCFNCGKE GHIAKNCRAP RKKGCWRCGR
EGHQMKDCTE RQANFLREDL AFLQGKAREF SSEQTRANSP TRRELQVWGG ENNSLSEAGA
DRQGTVSFNF PQITLWQRPL VTIRIGGQLK EALLDTGADD TVLEEMNLPG KWKPKMIGGI
GGFIKVRQYD QIPVEICGHK AIGTVLVGPT PVNIIGRNLL TQIGCTLNFP ISPIETVPVK
LKPGMDGPKV KQWPLTEEKI KALVEICTEM EKEGKISKIG PENPYNTPVF AIKKKDSTKW
RKLVDFRELN KRTQDFWEVQ LGIPHPAGLK KKKSVTVLDV GDAYFSVPLD KDFRKYTAFT
IPSINNETPG IRYQYNVLPQ GWKGSPAIFQ SSMTKILEPF RKQNPDIVIY QYMDDLYVGS
DLEIGQHRTK IEELRQHLLR WGFTTPDKKH QKEPPFLWMG YELHPDKWTV QPIMLPEKDS
WTVNDIQKLV GKLNWASQIY AGIKVKQLCK LLRGTKALTE VIPLTEEAEL ELAENREILK
EPVHEVYYDP SKDLVAEIQK QGQGQWTYQI YQEPFKNLKT GKYARMRGAH TNDVKQLTEA
VQKVSTESIV IWGKIPKFKL PIQKETWEAW WMEYWQATWI PEWEFVNTPP LVKLWYQLEK
EPIVGAETFY VDGAANRETK LGKAGYVTDR GRQKVVSIAD TTNQKTELQA IHLALQDSGL
EVNIVTDSQY ALGIIQAQPD KSESELVSQI IEQLIKKEKV YLAWVPAHKG IGGNEQVDKL
VSAGIRKVLF LNGIDKAQEE HEKYHSNWRA MASDFNLPPV VAKEIVASCD KCQLKGEAMH
GQVDCSPGIW QLDCTHLEGK IILVAVHVAS GYIEAEVIPA ETGQETAYFL LKLAGRWPVK
TIHTDNGSNF TSTTVKAACW WAGIKQEFGI PYNPQSQGVV ESMNNELKKI IGQVRDQAEH
LKTAVQMAVF IHNFKRKGGI GGYSAGERIV DIIATDIQTK ELQKQITKIQ NFRVYYRDNK
DPLWKGPAKL LWKGEGAVVI QDNSDIKVVP RRKAKIIRDY GKQMAGDDCV ASRQDED
