POL_HV1B5
ID POL_HV1B5 Reviewed; 1447 AA.
AC P04587;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 211.
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 BH5)
OS (HIV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11682;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2578615; DOI=10.1038/313277a0;
RA Ratner L., Haseltine W.A., Patarca R., Livak K.J., Starcich B.R.,
RA Josephs S.F., Doran E.R., Rafalski J.A., Whitehorn E.A., Baumeister K.,
RA Ivanoff L., Petteway S.R. Jr., Pearson M.L., Lautenberger J.A., Papas T.S.,
RA Ghrayeb J., Chang N.T., Gallo R.C., Wong-Staal F.;
RT "Complete nucleotide sequence of the AIDS virus, HTLV-III.";
RL Nature 313:277-284(1985).
RN [2]
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 [3]
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 [4]
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 [5]
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 [6]
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 [7]
RP X-RAY CRYSTALLOGRAPHY (2.22 ANGSTROMS) OF 501-599.
RX PubMed=7658450; DOI=10.1021/jm00018a023;
RA Thaisrivongs S., Watenpaugh K.D., Howe W.J., Tomich P.K., Dolak L.A.,
RA Chong K.-T., Tomich C.C., Tomasselli A.G., Turner S.R., Strohbach J.W.,
RA Mulichak A.M., Janakiraman M.N., Moon J.B., Lynn J.C., Horng M.-M.,
RA Hinshaw R.R., Curry K.A., Rothrock D.J.;
RT "Structure-based design of novel HIV protease inhibitors: carboxamide-
RT containing 4-hydroxycoumarins and 4-hydroxy-2-pyrones as potent nonpeptidic
RT inhibitors.";
RL J. Med. Chem. 38:3624-3637(1995).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 501-599 IN COMPLEX WITH THE
RP INHIBITOR SB203386.
RX PubMed=8756683; DOI=10.1021/bi960179j;
RA Hoog S.S., Towler E.M., Zhao B., Doyle M.L., Debouck C., Abdel-Meguid S.S.;
RT "Human immunodeficiency virus protease ligand specificity conferred by
RT residues outside of the active site cavity.";
RL Biochemistry 35:10279-10286(1996).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 501-599.
RX PubMed=9136873; DOI=10.1021/bi962729j;
RA Towler E.M., Thompson S.K., Tomaszek T., Debouck C.;
RT "Identification of a loop outside the active site cavity of the human
RT immunodeficiency virus proteases which confers inhibitor specificity.";
RL Biochemistry 36:5128-5133(1997).
RN [10]
RP STRUCTURE BY NMR OF 1160-1214.
RX PubMed=9228950; DOI=10.1038/nsb0797-567;
RA Cai M., Zheng R., Caffrey M., Craigie R., Clore G.M., Gronenborn A.M.;
RT "Solution structure of the N-terminal zinc binding domain of HIV-1
RT integrase.";
RL Nat. Struct. Biol. 4:567-577(1997).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 501-599 IN COMPLEX WITH THE
RP INHIBITOR SB203386.
RX PubMed=9692985; DOI=10.1021/bi980784h;
RA Swairjo M.A., Towler E.M., Debouck C., Abdel-Meguid S.S.;
RT "Structural role of the 30's loop in determining the ligand specificity of
RT the human immunodeficiency virus protease.";
RL Biochemistry 37:10928-10936(1998).
RN [12]
RP STRUCTURE BY NMR OF 1160-1205.
RX PubMed=9865962; DOI=10.1002/pro.5560071221;
RA Cai M., Huang Y., Caffrey M., Zheng R., Craigie R., Clore G.M.,
RA Gronenborn A.M.;
RT "Solution structure of the His12 --> Cys mutant of the N-terminal zinc
RT binding domain of HIV-1 integrase complexed to cadmium.";
RL Protein Sci. 7:2669-2674(1998).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) OF 501-599.
RX PubMed=11340661; DOI=10.1002/prot.1057;
RA Mahalingam B., Louis J.M., Hung J., Harrison R.W., Weber I.T.;
RT "Structural implications of drug-resistant mutants of HIV-1 protease: high-
RT resolution crystal structures of the mutant protease/substrate analogue
RT complexes.";
RL Proteins 43:455-464(2001).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 501-599 IN COMPLEX WITH
RP INHIBITORS.
RX PubMed=11170625; DOI=10.1021/jm001024j;
RA Schaal W., Karlsson A., Ahlsen G., Lindberg J., Andersson H.O.,
RA Danielson U.H., Classon B., Unge T., Samuelsson B., Hulten J., Hallberg A.,
RA Karlen A.;
RT "Synthesis and comparative molecular field analysis (CoMFA) of symmetric
RT and nonsymmetric cyclic sulfamide HIV-1 protease inhibitors.";
RL J. Med. Chem. 44:155-169(2001).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 501-599.
RX PubMed=12012342; DOI=10.1002/prot.10140;
RA Mahalingam B., Boross P.I., Wang Y.-F., Louis J.M., Fischer C.C.,
RA Tozser J., Harrison R.W., Weber I.T.;
RT "Combining mutations in HIV-1 protease to understand mechanisms of
RT resistance.";
RL Proteins 48:107-116(2002).
RN [16]
RP STRUCTURE BY NMR OF 501-594.
RX PubMed=12933791; DOI=10.1074/jbc.m307549200;
RA Ishima R., Torchia D.A., Lynch S.M., Gronenborn A.M., Louis J.M.;
RT "Solution structure of the mature HIV-1 protease monomer: insight into the
RT tertiary fold and stability of a precursor.";
RL J. Biol. Chem. 278:43311-43319(2003).
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.;
CC Name=Gag-Pol polyprotein;
CC IsoId=P04587-1; Sequence=Displayed;
CC Name=Gag polyprotein;
CC IsoId=P04593-1; 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; K02012; AAA44653.1; ALT_SEQ; Genomic_RNA.
DR PDB; 1BDL; X-ray; 2.80 A; A/B=501-599.
DR PDB; 1BDQ; X-ray; 2.50 A; A/B=501-599.
DR PDB; 1BDR; X-ray; 2.80 A; A/B=501-599.
DR PDB; 1FEJ; X-ray; 1.78 A; C/D=501-599.
DR PDB; 1FF0; X-ray; 1.85 A; C/D=501-599.
DR PDB; 1FFF; X-ray; 1.90 A; C/D=501-599.
DR PDB; 1FFI; X-ray; 1.70 A; C/D=501-599.
DR PDB; 1FG6; X-ray; 1.80 A; C/D=501-599.
DR PDB; 1FG8; X-ray; 1.85 A; C/D=501-599.
DR PDB; 1FGC; X-ray; 1.90 A; C/D=501-599.
DR PDB; 1G2K; X-ray; 1.95 A; A/B=501-599.
DR PDB; 1HPV; X-ray; 1.90 A; A/B=501-599.
DR PDB; 1HVJ; X-ray; 2.00 A; A/B=501-599.
DR PDB; 1HVS; X-ray; 2.25 A; A/B=501-599.
DR PDB; 1K1T; X-ray; 1.20 A; A/B=501-599.
DR PDB; 1K1U; X-ray; 1.55 A; A/B=501-599.
DR PDB; 1K2B; X-ray; 1.70 A; A/B=501-599.
DR PDB; 1K2C; X-ray; 2.20 A; A/B=501-599.
DR PDB; 1ODX; X-ray; 2.00 A; A/B=501-599.
DR PDB; 1Q9P; NMR; -; A=501-595.
DR PDB; 1TCX; X-ray; 2.30 A; A/B=501-599.
DR PDB; 1WJE; NMR; -; A/B=1160-1205.
DR PDB; 1WJF; NMR; -; A/B=1160-1214.
DR PDB; 2AOC; X-ray; 1.30 A; A/B=501-599.
DR PDB; 2AOD; X-ray; 1.40 A; A/B=501-599.
DR PDB; 2AOE; X-ray; 1.54 A; A/B=501-599.
DR PDB; 2AOF; X-ray; 1.32 A; A/B=501-599.
DR PDB; 2AOG; X-ray; 1.10 A; A/B=501-599.
DR PDB; 2AOH; X-ray; 1.42 A; A/B=501-599.
DR PDB; 2AOI; X-ray; 1.40 A; A/B=501-599.
DR PDB; 2AOJ; X-ray; 1.60 A; A/B=501-599.
DR PDB; 2AVM; X-ray; 1.10 A; A/B=501-599.
DR PDB; 2AVO; X-ray; 1.10 A; A/B=501-599.
DR PDB; 2AVQ; X-ray; 1.30 A; A/B=501-599.
DR PDB; 2AVS; X-ray; 1.10 A; A/B=501-599.
DR PDB; 2AVV; X-ray; 1.50 A; A/B/D/E=501-599.
DR PDB; 2BPV; X-ray; 1.90 A; A/B=501-599.
DR PDB; 2BPW; X-ray; 2.80 A; A/B=501-599.
DR PDB; 2BPX; X-ray; 2.80 A; A/B=501-599.
DR PDB; 2BPY; X-ray; 1.90 A; A/B=501-599.
DR PDB; 2BPZ; X-ray; 2.50 A; A/B=501-599.
DR PDB; 2F80; X-ray; 1.45 A; A/B=501-599.
DR PDB; 2F81; X-ray; 1.25 A; A/B=501-599.
DR PDB; 2F8G; X-ray; 1.22 A; A/B=501-599.
DR PDB; 2NMY; X-ray; 1.10 A; A/B=501-598.
DR PDB; 2NMZ; X-ray; 0.97 A; A/B=501-598.
DR PDB; 2NNK; X-ray; 1.25 A; A/B=501-598.
DR PDB; 2NNP; X-ray; 1.20 A; A/B=501-598.
DR PDB; 2R38; X-ray; 1.81 A; A/B=501-599.
DR PDB; 2R3T; X-ray; 1.80 A; A/B=501-599.
DR PDB; 2R3W; X-ray; 1.92 A; A/B=501-599.
DR PDB; 2Z54; X-ray; 2.31 A; A/B=501-599.
DR PDB; 3B7V; X-ray; 1.46 A; A/B=501-599.
DR PDB; 3B80; X-ray; 1.50 A; A/B=501-599.
DR PDB; 3BC4; X-ray; 1.82 A; A=501-599.
DR PDB; 3BGB; X-ray; 1.90 A; A/B=501-599.
DR PDB; 3BGC; X-ray; 1.80 A; A/B=501-599.
DR PDB; 3CYW; X-ray; 1.40 A; A/B=501-599.
DR PDB; 3CYX; X-ray; 1.20 A; A/B=501-599.
DR PDB; 3D1X; X-ray; 1.05 A; A/B=501-599.
DR PDB; 3D1Y; X-ray; 1.05 A; A/B=501-599.
DR PDB; 3D1Z; X-ray; 1.30 A; A/B=501-599.
DR PDB; 3D20; X-ray; 1.05 A; A/B=501-599.
DR PDB; 3OXC; X-ray; 1.16 A; A/B=501-598.
DR PDB; 6B36; X-ray; 1.63 A; A/B=501-599.
DR PDB; 6B38; X-ray; 1.48 A; A/B=501-599.
DR PDB; 6B3C; X-ray; 1.60 A; A/B=501-599.
DR PDB; 6B3F; X-ray; 1.46 A; A/B=501-599.
DR PDB; 6B3G; X-ray; 1.50 A; A/B=501-599.
DR PDB; 6B3H; X-ray; 1.62 A; A/B=501-599.
DR PDBsum; 1BDL; -.
DR PDBsum; 1BDQ; -.
DR PDBsum; 1BDR; -.
DR PDBsum; 1FEJ; -.
DR PDBsum; 1FF0; -.
DR PDBsum; 1FFF; -.
DR PDBsum; 1FFI; -.
DR PDBsum; 1FG6; -.
DR PDBsum; 1FG8; -.
DR PDBsum; 1FGC; -.
DR PDBsum; 1G2K; -.
DR PDBsum; 1HPV; -.
DR PDBsum; 1HVJ; -.
DR PDBsum; 1HVS; -.
DR PDBsum; 1K1T; -.
DR PDBsum; 1K1U; -.
DR PDBsum; 1K2B; -.
DR PDBsum; 1K2C; -.
DR PDBsum; 1ODX; -.
DR PDBsum; 1Q9P; -.
DR PDBsum; 1TCX; -.
DR PDBsum; 1WJE; -.
DR PDBsum; 1WJF; -.
DR PDBsum; 2AOC; -.
DR PDBsum; 2AOD; -.
DR PDBsum; 2AOE; -.
DR PDBsum; 2AOF; -.
DR PDBsum; 2AOG; -.
DR PDBsum; 2AOH; -.
DR PDBsum; 2AOI; -.
DR PDBsum; 2AOJ; -.
DR PDBsum; 2AVM; -.
DR PDBsum; 2AVO; -.
DR PDBsum; 2AVQ; -.
DR PDBsum; 2AVS; -.
DR PDBsum; 2AVV; -.
DR PDBsum; 2BPV; -.
DR PDBsum; 2BPW; -.
DR PDBsum; 2BPX; -.
DR PDBsum; 2BPY; -.
DR PDBsum; 2BPZ; -.
DR PDBsum; 2F80; -.
DR PDBsum; 2F81; -.
DR PDBsum; 2F8G; -.
DR PDBsum; 2NMY; -.
DR PDBsum; 2NMZ; -.
DR PDBsum; 2NNK; -.
DR PDBsum; 2NNP; -.
DR PDBsum; 2R38; -.
DR PDBsum; 2R3T; -.
DR PDBsum; 2R3W; -.
DR PDBsum; 2Z54; -.
DR PDBsum; 3B7V; -.
DR PDBsum; 3B80; -.
DR PDBsum; 3BC4; -.
DR PDBsum; 3BGB; -.
DR PDBsum; 3BGC; -.
DR PDBsum; 3CYW; -.
DR PDBsum; 3CYX; -.
DR PDBsum; 3D1X; -.
DR PDBsum; 3D1Y; -.
DR PDBsum; 3D1Z; -.
DR PDBsum; 3D20; -.
DR PDBsum; 3OXC; -.
DR PDBsum; 6B36; -.
DR PDBsum; 6B38; -.
DR PDBsum; 6B3C; -.
DR PDBsum; 6B3F; -.
DR PDBsum; 6B3G; -.
DR PDBsum; 6B3H; -.
DR BMRB; P04587; -.
DR SMR; P04587; -.
DR DrugBank; DB07910; (2S)-2-amino-3-phenylpropane-1,1-diol.
DR DrugBank; DB08115; 2-aminoethyl naphthalen-1-ylacetate.
DR MEROPS; A02.001; -.
DR ABCD; P04587; 2 sequenced antibodies.
DR EvolutionaryTrace; P04587; -.
DR PRO; PR:P04587; -.
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 Repeat; Ribosomal frameshifting; RNA-binding; RNA-directed DNA polymerase;
KW Transferase; Viral genome integration; Viral nucleoprotein;
KW Viral penetration into host nucleus; Viral release from host cell; Virion;
KW Virion maturation; Virus entry into host cell; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed; by host"
FT /evidence="ECO:0000250"
FT CHAIN 2..1447
FT /note="Gag-Pol polyprotein"
FT /id="PRO_0000261262"
FT CHAIN 2..132
FT /note="Matrix protein p17"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042294"
FT CHAIN 133..363
FT /note="Capsid protein p24"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042295"
FT PEPTIDE 364..377
FT /note="Spacer peptide 1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042296"
FT CHAIN 378..432
FT /note="Nucleocapsid protein p7"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042297"
FT PEPTIDE 433..440
FT /note="Transframe peptide"
FT /evidence="ECO:0000255"
FT /id="PRO_0000246711"
FT CHAIN 441..500
FT /note="p6-pol"
FT /evidence="ECO:0000255"
FT /id="PRO_0000042298"
FT CHAIN 501..599
FT /note="Protease"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038648"
FT CHAIN 600..1159
FT /note="Reverse transcriptase/ribonuclease H"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042299"
FT CHAIN 600..1039
FT /note="p51 RT"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042300"
FT CHAIN 1040..1159
FT /note="p15"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042301"
FT CHAIN 1160..1447
FT /note="Integrase"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042302"
FT DOMAIN 520..589
FT /note="Peptidase A2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00275"
FT DOMAIN 643..833
FT /note="Reverse transcriptase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT DOMAIN 1033..1156
FT /note="RNase H type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT DOMAIN 1213..1363
FT /note="Integrase catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00457"
FT ZN_FING 390..407
FT /note="CCHC-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT ZN_FING 411..428
FT /note="CCHC-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT ZN_FING 1162..1203
FT /note="Integrase-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT DNA_BIND 1382..1429
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..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 189..227
FT /note="Interaction with human PPIA/CYPA and NUP153"
FT /evidence="ECO:0000250|UniProtKB:P12497"
FT REGION 277..363
FT /note="Dimerization/Multimerization of capsid protein p24"
FT /evidence="ECO:0000250|UniProtKB:P04585"
FT REGION 446..493
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 501..505
FT /note="Dimerization of protease"
FT /evidence="ECO:0000250|UniProtKB:P04585"
FT REGION 549..555
FT /note="Dimerization of protease"
FT /evidence="ECO:0000250|UniProtKB:P04585"
FT REGION 588..600
FT /note="Dimerization of protease"
FT /evidence="ECO:0000250|UniProtKB:P04585"
FT REGION 826..834
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 997..1013
FT /note="Tryptophan repeat motif"
FT /evidence="ECO:0000250"
FT ACT_SITE 525
FT /note="For protease activity; shared with dimeric partner"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT BINDING 709
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 784
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 785
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 1042
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 1077
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 1097
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 1148
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 1171
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT BINDING 1175
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT BINDING 1199
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT BINDING 1202
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT BINDING 1223
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 1275
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 1311
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 132..133
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 221..222
FT /note="Cis/trans isomerization of proline peptide bond; by
FT human PPIA/CYPA"
FT /evidence="ECO:0000250"
FT SITE 363..364
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 377..378
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 432..433
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000255"
FT SITE 440..441
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 500..501
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 599..600
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 1000
FT /note="Essential for RT p66/p51 heterodimerization"
FT /evidence="ECO:0000250"
FT SITE 1013
FT /note="Essential for RT p66/p51 heterodimerization"
FT /evidence="ECO:0000250"
FT SITE 1039..1040
FT /note="Cleavage; by viral protease; partial"
FT /evidence="ECO:0000250"
FT SITE 1159..1160
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT MOD_RES 132
FT /note="Phosphotyrosine; by host"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-myristoyl glycine; by host"
FT /evidence="ECO:0000250"
FT STRAND 502..504
FT /evidence="ECO:0007829|PDB:1BDQ"
FT STRAND 505..507
FT /evidence="ECO:0007829|PDB:3D1X"
FT STRAND 510..515
FT /evidence="ECO:0007829|PDB:3D1X"
FT STRAND 518..524
FT /evidence="ECO:0007829|PDB:3D1X"
FT STRAND 532..535
FT /evidence="ECO:0007829|PDB:2AVS"
FT STRAND 542..549
FT /evidence="ECO:0007829|PDB:3D1X"
FT STRAND 552..566
FT /evidence="ECO:0007829|PDB:3D1X"
FT STRAND 569..578
FT /evidence="ECO:0007829|PDB:3D1X"
FT STRAND 581..585
FT /evidence="ECO:0007829|PDB:1K2B"
FT HELIX 587..590
FT /evidence="ECO:0007829|PDB:3D1X"
FT HELIX 591..593
FT /evidence="ECO:0007829|PDB:3D1X"
FT STRAND 596..598
FT /evidence="ECO:0007829|PDB:3D1X"
FT HELIX 1163..1174
FT /evidence="ECO:0007829|PDB:1WJE"
FT HELIX 1178..1185
FT /evidence="ECO:0007829|PDB:1WJE"
FT HELIX 1189..1198
FT /evidence="ECO:0007829|PDB:1WJE"
FT HELIX 1200..1203
FT /evidence="ECO:0007829|PDB:1WJE"
FT STRAND 1204..1207
FT /evidence="ECO:0007829|PDB:1WJF"
SQ SEQUENCE 1447 AA; 163265 MW; F4D0290A5010027B CRC64;
MGARASVLSG GELDRWEKIR LRPGGKKKYK LKHIVWASRE LERFAVNPGL LETSEGCRQI
LGQLQPSLQT GSEELRSLYN TVATLYCVHQ RIEIKDTKEA LDKIEEEQNK SKKKAQQAAA
DTGHSSQVSQ NYPIVQNIQG QMVHQAISPR TLNAWVKVVE EKAFSPEVIP MFSALSEGAT
PQDLNTMLNT VGGHQAAMQM LKETINEEAA EWDRVHPVHA GPIAPGQMRE PRGSDIAGTT
STLQEQIGWM TNNPPIPVGE IYKRWIILGL NKIVRMYSPT SILDIRQGPK EPFRDYVDRF
YKTLRAEQAS QEVKNWMTET LLVQNANPDC KTILKALGPA ATLEEMMTAC QGVGGPGHKA
RVLAEAMSQV TNSTTIMMQR GNFRNQRKIV KCFNCGKEGH IARNCKAPRK KGCWKCGKEG
HQMKDCTERQ ANFLREDLAF LQGKAREFSS EQTRANSPTI SSEQTRANSP TRRELQVWGR
DNNSPSEAGA DRQGTVSFNF PQITLWQRPL VTIKIGGQLK EALLDTGADD TVLEEMSLPG
RWKPKMIGGI GGFIKVRQYD QILIEICGHK AIGTVLVGPT PVNIIGRNLL TQIGCTLNFP
ISPIETVPVK LKPGMDGPKV KQWPLTEEKI KALVEICTEM EKEGKISKIG PENPYNTPVF
AIKKKDSTKW RKLVDFRELN RRTQDFWEVQ LGIPHPAGLK KKKSVTVLDV GDAYFSVPLD
EDFRKYTAFT IPSINNETPG SGYQYNVLPQ GWKGSPAIFQ SSMTKILEPF RKQNPDIVIY
QYMDDLYVGS DLEIGQHRTK IEELRQHLLR WGFTTPDKKH QKEPPFLWMG YELHPDKWTI
QPIVLPEKDS WTVNDIQKLV GKLNWASQIY PGIKVRQLCK LLRGTKALTE VIPLTEEAEL
ELAENREILK EPVHGVYYDP SKDLIAEIQK QGQGQWTYQI YQEPFKNLKT GKYARMRGAH
TNDVKQLTEA VQKITTESIV IWGKTPKFKL PIQKETWETW WTEYWQATWI PEWEFVNTPP
LVKLWYQLEK EPIVGAETFY VDGAASRETK LGKAGYVTNR GRQKVVTLTH TTNQKTELQA
IHLALQDSGL EVNIVTDSQY ALGIIQAQPD KSESELVNQI IEQLIKKEKV YLAWVPAHKG
IGGNEQVDKL VSAGIRKILF LDGIDKAQEE HEKYHSNWRA MASDFNLPPV VAKEIVASCD
KCQLKGEAMH GQVDCSPGIW QLDCTHLEGK VILVAVHVAS GYIEAEVIPA ETGQETAYFL
LKLAGRWPVK TIHTDNGSNF TSATVKAACW WAGIKQEFGI PYNPQSQGVV ESMNKELKKI
IGQVRDQAEH LKTAVQMAVF IHNFKRKGGI GGYSAGERIV DIIATDIQTK ELQKQITKIQ
NFRVYYRDSR NPLWKGPAKL LWKGEGAVVI QDNSDIKVVP RRKAKIIRDY GKQMAGDDCV
ASRQDED
