POL_SIVM1
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 03-AUG-2022, entry version 177.
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.
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 shutt 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; Genome.
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; 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; IPR000721; Gag_p24_N.
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; 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; 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; 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
