ID   POL_SIVM1               Reviewed;        1448 AA.
AC   P05896;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   02-OCT-2007, sequence version 2.
DT   27-MAR-2024, entry version 185.
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=Nucleocapsid protein p7;
DE              Short=NC;
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   Simian immunodeficiency virus (isolate Mm142-83) (SIV-mac) (Simian
OS   immunodeficiency virus rhesus monkey).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Simian immunodeficiency virus.
OX   NCBI_TaxID=11733;
OH   NCBI_TaxID=9527; Cercopithecidae (Old World monkeys).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3649576; DOI=10.1038/328543a0;
RA   Chakrabarti L., Guyader M., Alizon M., Daniel M.D., Desrosiers R.C.,
RA   Tiollais P., Sonigo P.;
RT   "Sequence of simian immunodeficiency virus from macaque and its
RT   relationship to other human and simian retroviruses.";
RL   Nature 328:543-547(1987).
RN   [2]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 498-595.
RX   PubMed=9485411; DOI=10.1021/bi9716074;
RA   Rose R.B., Craik C.S., Stroud R.M.;
RT   "Domain flexibility in retroviral proteases: structural implications for
RT   drug resistant mutations.";
RL   Biochemistry 37:2607-2621(1998).
CC   -!- FUNCTION: Gag-Pol polyprotein and Gag polyprotein may regulate their
CC       own translation, by the binding genomic RNA in the 5'-UTR. At low
CC       concentration, Gag-Pol and Gag would promote translation, whereas at
CC       high concentration, the polyproteins encapsidate genomic RNA and then
CC       shut off translation (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: Matrix protein p17 has two main functions: in infected cell,
CC       it targets Gag and Gag-pol polyproteins to the plasma membrane via a
CC       multipartite membrane-binding signal, that includes its
CC       myristointegration complex. The myristoylation signal and the NLS exert
CC       conflicting influences its subcellular localization. The key regulation
CC       of these motifs might be phosphorylation of a portion of MA molecules
CC       on the C-terminal tyrosine at the time of virus maturation, by virion-
CC       associated cellular tyrosine kinase. Implicated in the release from
CC       host cell mediated by Vpu (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: Capsid protein p24 forms the conical core that encapsulates
CC       the genomic RNA-nucleocapsid complex in the virion. The core is
CC       constituted by capsid protein hexamer subunits. The core is
CC       disassembled soon after virion entry. Interaction with host PPIA/CYPA
CC       protects the virus from restriction by host TRIM5-alpha and from an
CC       unknown antiviral activity in host cells. This capsid restriction by
CC       TRIM5 is one of the factors which restricts SIV to the simian species
CC       (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: Nucleocapsid protein p7 encapsulates and protects viral
CC       dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc
CC       fingers. Facilitates rearangement of nucleic acid secondary structure
CC       during retrotranscription of genomic RNA. This capability is referred
CC       to as nucleic acid chaperone activity (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: The aspartyl protease mediates proteolytic cleavages of Gag
CC       and Gag-Pol polyproteins during or shortly after the release of the
CC       virion from the plasma membrane. Cleavages take place as an ordered,
CC       step-wise cascade to yield mature proteins. This process is called
CC       maturation. Displays maximal activity during the budding process just
CC       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 (By similarity).
CC       {ECO:0000255|PROSITE-ProRule:PRU00275}.
CC   -!- FUNCTION: Reverse transcriptase/ribonuclease H (RT) is a
CC       multifunctional enzyme that converts the viral dimeric RNA genome into
CC       dsDNA in the cytoplasm, shortly after virus entry into the cell. This
CC       enzyme displays a DNA polymerase activity that can copy either DNA or
CC       RNA templates, and a ribonuclease H (RNase H) activity that cleaves the
CC       RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5'
CC       endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires
CC       many steps. A tRNA binds to the primer-binding site (PBS) situated at
CC       the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to
CC       perform a short round of RNA-dependent minus-strand DNA synthesis. The
CC       reading proceeds through the U5 region and ends after the repeated (R)
CC       region which is present at both ends of viral RNA. The portion of the
CC       RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA
CC       product attached to the tRNA primer. This ssDNA/tRNA hybridizes with
CC       the identical R region situated at the 3' end of viral RNA. This
CC       template exchange, known as minus-strand DNA strong stop transfer, can
CC       be either intra- or intermolecular. RT uses the 3' end of this newly
CC       synthesized short ssDNA to perform the RNA-dependent minus-strand DNA
CC       synthesis of the whole template. RNase H digests the RNA template
CC       except for two polypurine tracts (PPTs) situated at the 5'-end and near
CC       the center of the genome. It is not clear if both polymerase and RNase
CC       H activities are simultaneous. RNase H can probably proceed both in a
CC       polymerase-dependent (RNA cut into small fragments by the same RT
CC       performing DNA synthesis) and a polymerase-independent mode (cleavage
CC       of remaining RNA fragments by free RTs). Secondly, RT performs DNA-
CC       directed plus-strand DNA synthesis using the PPTs that have not been
CC       removed by RNase H as primers. PPTs and tRNA primers are then removed
CC       by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a
CC       circular dsDNA intermediate. Strand displacement synthesis by RT to the
CC       PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral
CC       genome that includes long terminal repeats (LTRs) at both ends (By
CC       similarity). {ECO:0000250}.
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 SIV genome, a 5 bp duplication of host DNA is produced at
CC       the ends of SIV integration. Alternatively, Integrase may catalyze the
CC       excision of viral DNA just after strand transfer, this is termed
CC       disintegration (By similarity). {ECO:0000250}.
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;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3'-end directed exonucleolytic cleavage of viral RNA-DNA
CC         hybrid.; EC=3.1.13.2;
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: The viral protease is inhibited by many synthetic
CC       protease inhibitors (PIs), such as amprenavir, atazanavir, indinavir,
CC       loprinavir, nelfinavir, ritonavir and saquinavir. RT can be inhibited
CC       either by nucleoside RT inhibitors (NRTIs) or by non nucleoside RT
CC       inhibitors (NNRTIs). NRTIs act as chain terminators, whereas NNRTIs
CC       inhibit DNA polymerization by binding a small hydrophobic pocket near
CC       the RT active site and inducing an allosteric change in this region.
CC       Classical NRTIs are abacavir, adefovir (PMEA), didanosine (ddI),
CC       lamivudine (3TC), stavudine (d4T), tenofovir (PMPA), zalcitabine (ddC),
CC       and zidovudine (AZT). Classical NNRTIs are atevirdine (BHAP U-87201E),
CC       delavirdine, efavirenz (DMP-266), emivirine (I-EBU), and nevirapine
CC       (BI-RG-587). The tritherapies used as a basic effective treatment of
CC       AIDS associate two NRTIs and one NNRTI. Use of protease inhibitors in
CC       tritherapy regimens permit more ambitious therapeutic strategies.
CC   -!- SUBUNIT: [Matrix protein p17]: Homotrimer. Interacts with gp41 (via C-
CC       terminus). {ECO:0000250|UniProtKB:P04591,
CC       ECO:0000250|UniProtKB:P12493}.
CC   -!- SUBUNIT: [Protease]: Homodimer. The active site consists of two apposed
CC       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). Heterodimerization of RT is essential for DNA
CC       polymerase activity. Despite the sequence identities, p66 RT and p51 RT
CC       have distinct folding. {ECO:0000250|UniProtKB:P03366}.
CC   -!- SUBUNIT: [Integrase]: Homotetramer; may further associate as a
CC       homohexadecamer (By similarity). {ECO:0000250|UniProtKB:P03367}.
CC   -!- SUBCELLULAR LOCATION: [Matrix protein p17]: Virion {ECO:0000305}. Host
CC       nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}. Host cell membrane
CC       {ECO:0000305}; Lipid-anchor {ECO:0000305}. Note=Following virus entry,
CC       the nuclear localization signal (NLS) of the matrix protein
CC       participates with Vpr to the nuclear localization of the viral genome.
CC       During virus production, the nuclear export activity of the matrix
CC       protein counteracts the NLS to maintain the Gag and Gag-Pol
CC       polyproteins in the cytoplasm, thereby directing unspliced RNA to the
CC       plasma membrane (By similarity). {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=P05896-1; Sequence=Displayed;
CC       Name=Gag polyprotein;
CC         IsoId=P05894-1; Sequence=External;
CC   -!- DOMAIN: The p66 RT is structured in five subdomains: finger, palm,
CC       thumb, connection and RNase H. Within the palm subdomain, the 'primer
CC       grip' region is thought to be involved in the positioning of the primer
CC       terminus for accommodating the incoming nucleotide. The RNase H domain
CC       stabilizes the association of RT with primer-template (By similarity).
CC       {ECO:0000250}.
CC   -!- DOMAIN: The tryptophan repeat motif is involved in RT p66/p51
CC       dimerization. {ECO:0000250}.
CC   -!- PTM: Specific enzymatic cleavages by the viral protease yield mature
CC       proteins. The protease is released by autocatalytic cleavage. The
CC       polyprotein is cleaved during and after budding, this process is termed
CC       maturation. Proteolytic cleavage of p66 RT removes the RNase H domain
CC       to yield the p51 RT subunit. {ECO:0000255|PROSITE-ProRule:PRU00405}.
CC   -!- PTM: Capsid protein p24 is phosphorylated.
CC   -!- MISCELLANEOUS: This is a macaque isolate.
CC   -!- MISCELLANEOUS: The reverse transcriptase is an error-prone enzyme that
CC       lacks a proof-reading function. High mutations rate is a direct
CC       consequence of this characteristic. RT also displays frequent template
CC       switching leading to high recombination rate. Recombination mostly
CC       occurs between homologous regions of the two copackaged RNA genomes. If
CC       these two RNA molecules derive from different viral strains, reverse
CC       transcription will give rise to highly recombinated proviral DNAs.
CC   -!- MISCELLANEOUS: [Isoform Gag-Pol polyprotein]: Produced by -1 ribosomal
CC       frameshifting.
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DR   EMBL; Y00277; CAA68380.1; -; Genomic_DNA.
DR   PDB; 1AZ5; X-ray; 2.00 A; A=498-595.
DR   PDB; 1C6V; X-ray; 3.00 A; A/B/C/D=1205-1368.
DR   PDB; 1SIV; X-ray; 2.50 A; A/B=498-596.
DR   PDB; 1TCW; X-ray; 2.40 A; A/B=498-596.
DR   PDB; 1YTI; X-ray; 2.20 A; A=498-595.
DR   PDB; 1YTJ; X-ray; 2.50 A; A=498-595.
DR   PDBsum; 1AZ5; -.
DR   PDBsum; 1C6V; -.
DR   PDBsum; 1SIV; -.
DR   PDBsum; 1TCW; -.
DR   PDBsum; 1YTI; -.
DR   PDBsum; 1YTJ; -.
DR   SMR; P05896; -.
DR   DrugBank; DB04191; Skf 107457.
DR   EvolutionaryTrace; P05896; -.
DR   PRO; PR:P05896; -.
DR   Proteomes; UP000007220; Segment.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
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:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-KW.
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: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: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; 3.30.70.270; -; 3.
DR   Gene3D; 2.40.70.10; Acid Proteases; 1.
DR   Gene3D; 3.10.10.10; HIV Type 1 Reverse Transcriptase, subunit A, domain 1; 1.
DR   Gene3D; 1.10.375.10; Human Immunodeficiency Virus Type 1 Capsid Protein; 1.
DR   Gene3D; 1.10.150.90; Immunodeficiency lentiviruses, gag gene matrix protein p17; 1.
DR   Gene3D; 2.30.30.10; Integrase, C-terminal domain superfamily, retroviral; 1.
DR   Gene3D; 3.30.420.10; Ribonuclease H-like superfamily/Ribonuclease H; 2.
DR   Gene3D; 1.20.5.760; Single helix bin; 1.
DR   Gene3D; 4.10.60.10; Zinc finger, CCHC-type; 1.
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   PANTHER; PTHR41694; ENDOGENOUS RETROVIRUS GROUP K MEMBER POL PROTEIN; 1.
DR   PANTHER; PTHR41694:SF3; RNA-DIRECTED DNA POLYMERASE-RELATED; 1.
DR   Pfam; PF00540; Gag_p17; 1.
DR   Pfam; PF00607; Gag_p24; 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; 1.
DR   PRINTS; PR00234; HIV1MATRIX.
DR   SMART; SM00343; ZnF_C2HC; 2.
DR   SUPFAM; SSF50630; Acid proteases; 1.
DR   SUPFAM; SSF50122; DNA-binding domain of retroviral integrase; 1.
DR   SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR   SUPFAM; SSF46919; N-terminal Zn binding domain of HIV integrase; 1.
DR   SUPFAM; SSF47836; Retroviral matrix proteins; 1.
DR   SUPFAM; SSF47353; Retrovirus capsid dimerization domain-like; 1.
DR   SUPFAM; SSF47943; Retrovirus capsid protein, N-terminal core domain; 1.
DR   SUPFAM; SSF57756; Retrovirus zinc finger-like domains; 1.
DR   SUPFAM; SSF53098; Ribonuclease H-like; 2.
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; Aspartyl protease; Capsid protein; DNA integration;
KW   DNA recombination; 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 gene expression shutoff by virus; Host membrane;
KW   Host nucleus; Host-virus interaction; Hydrolase; Lipoprotein; Magnesium;
KW   Membrane; Metal-binding; Multifunctional enzyme; Myristate; Nuclease;
KW   Nucleotidyltransferase; Phosphoprotein; Protease; Repeat;
KW   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..1448
FT                   /note="Gag-Pol polyprotein"
FT                   /id="PRO_0000306035"
FT   CHAIN           2..135
FT                   /note="Matrix protein p17"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000306036"
FT   CHAIN           136..364
FT                   /note="Capsid protein p24"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000306037"
FT   CHAIN           365..433
FT                   /note="Nucleocapsid protein p7"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000306038"
FT   CHAIN           434..500
FT                   /note="p6-pol"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000306039"
FT   CHAIN           501..596
FT                   /note="Protease"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000306040"
FT   CHAIN           597..1155
FT                   /note="Reverse transcriptase/ribonuclease H"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000306041"
FT   CHAIN           597..1035
FT                   /note="p51 RT"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000306042"
FT   CHAIN           1036..1155
FT                   /note="p15"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000306043"
FT   CHAIN           1156..1448
FT                   /note="Integrase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000306044"
FT   DOMAIN          517..586
FT                   /note="Peptidase A2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00275"
FT   DOMAIN          640..830
FT                   /note="Reverse transcriptase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT   DOMAIN          1029..1152
FT                   /note="RNase H type-1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT   DOMAIN          1209..1359
FT                   /note="Integrase catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00457"
FT   ZN_FING         391..408
FT                   /note="CCHC-type 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT   ZN_FING         412..429
FT                   /note="CCHC-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT   ZN_FING         1158..1199
FT                   /note="Integrase-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT   DNA_BIND        1378..1425
FT                   /note="Integrase-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00506"
FT   REGION          218..237
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          440..461
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          823..831
FT                   /note="RT 'primer grip'"
FT                   /evidence="ECO:0000250"
FT   REGION          1426..1448
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
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           993..1009
FT                   /note="Tryptophan repeat motif"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        522
FT                   /note="For protease activity; shared with dimeric partner"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT   BINDING         706
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         781
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         782
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         1038
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         1073
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         1093
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         1144
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         1167
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT   BINDING         1171
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT   BINDING         1195
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT   BINDING         1198
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT   BINDING         1219
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         1271
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   SITE            135..136
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000250"
FT   SITE            364..365
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000250"
FT   SITE            433..434
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            596..597
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000250"
FT   SITE            996
FT                   /note="Essential for RT p66/p51 heterodimerization"
FT                   /evidence="ECO:0000250"
FT   SITE            1009
FT                   /note="Essential for RT p66/p51 heterodimerization"
FT                   /evidence="ECO:0000250"
FT   SITE            1035..1036
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000250"
FT   SITE            1155..1156
FT                   /note="Cleavage; by viral protease"
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:1AZ5"
FT   STRAND          507..512
FT                   /evidence="ECO:0007829|PDB:1AZ5"
FT   STRAND          515..521
FT                   /evidence="ECO:0007829|PDB:1AZ5"
FT   STRAND          525..527
FT                   /evidence="ECO:0007829|PDB:1YTI"
FT   STRAND          540..544
FT                   /evidence="ECO:0007829|PDB:1AZ5"
FT   STRAND          551..563
FT                   /evidence="ECO:0007829|PDB:1AZ5"
FT   STRAND          566..575
FT                   /evidence="ECO:0007829|PDB:1AZ5"
FT   HELIX           584..589
FT                   /evidence="ECO:0007829|PDB:1AZ5"
FT   STRAND          593..595
FT                   /evidence="ECO:0007829|PDB:1TCW"
SQ   SEQUENCE   1448 AA;  163372 MW;  460D13331B3E68E5 CRC64;
     MGARNSVLSG KKADELEKIR LRPGGKKKYM LKHVVWAANE LDRFGLAESL LENKEGCQKI
     LSVLAPLVPT GSENLKSLYN TVCVIWCIHA EEKVKHTEEA KQIVQRHLVM ETGTAETMPK
     TSRPTAPFSG RGGNYPVQQI GGNYTHLPLS PRTLNAWVKL IEEKKFGAEV VSGFQALSEG
     CLPYDINQML NCVGDHQAAM QIIRDIINEE AADWDLQHPQ QAPQQGQLRE PSGSDIAGTT
     STVEEQIQWM YRQQNPIPVG NIYRRWIQLG LQKCVRMYNP TNILDVKQGP KEPFQSYVDR
     FYKSLRAEQT DPAVKNWMTQ TLLIQNANPD CKLVLKGLGT NPTLEEMLTA CQGVGGPGQK
     ARLMAEALKE ALAPAPIPFA AAQQKGPRKP IKCWNCGKEG HSARQCRAPR RQGCWKCGKM
     DHVMAKCPNR QAGFFRPWPL GKEAPQFPHG SSASGADANC SPRRTSCGSA KELHALGQAA
     ERKQREALQG GDRGFAAPQF SLWRRPVVTA HIEGQPVEVL LDTGADDSIV TGIELGPHYT
     PKIVGGIGGF INTKEYKNVE IEVLGKRIKG TIMTGDTPIN IFGRNLLTAL GMSLNLPIAK
     VEPVKSPLKP GKDGPKLKQW PLSKEKIVAL REICEKMEKD GQLEEAPPTN PYNTPTFAIK
     KKDKNKWRML IDFRELNRVT QDFTEVQLGI PHPAGLAKRK RITVLDIGDA YFSIPLDEEF
     RQYTAFTLPS VNNAEPGKRY IYKVLPQGWK GSPAIFQYTM RHVLEPFRKA NPDVTLVQYM
     DDILIASDRT DLEHDRVVLQ LKELLNSIGF SSPEEKFQKD PPFQWMGYEL WPTKWKLQKI
     ELPQRETWTV NDIQKLVGVL NWAAQIYPGI KTKHLCRLIR GKMTLTEEVQ WTEMAEAEYE
     ENKIILSQEQ EGCYYQESKP LEATVIKSQD NQWSYKIHQE DKILKVGKFA KIKNTHTNGV
     RLLAHVIQKI GKEAIVIWGQ VPKFHLPVEK DVWEQWWTDY WQVTWIPEWD FISTPPLVRL
     VFNLVKDPIE GEETYYVDGS CSKQSKEGKA GYITDRGKDK VKVLEQTTNQ QAELEAFLMA
     LTDSGPKANI IVDSQYVMGI ITGCPTESES RLVNQIIEEM IKKTEIYVAW VPAHKGIGGN
     QEIDHLVSQG IRQVLFLEKI EPAQEEHSKY HSNIKELVFK FGLPRLVAKQ IVDTCDKCHQ
     KGEAIHGQVN SDLGTWQMDC THLEGKIVIV AVHVASGFIE AEVIPQETGR QTALFLLKLA
     SRWPITHLHT DNGANFASQE VKMVAWWAGI EHTFGVPYNP QSQGVVEAMN HHLKNQIDRI
     REQANSVETI VLMAVHCMNF KRRGGIGDMT PAERLINMIT TEQEIQFQQS KNSKFKNFRV
     YYREGRDQLW KGPGELLWKG EGAVILKVGT DIKVVPRRKA KIIKDYGGGK EMDSSSHMED
     TGEAREVA
//