POL_FOAMV
ID POL_FOAMV Reviewed; 1143 AA.
AC P14350; O12528; O12817; Q76U32; Q98835;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Pro-Pol polyprotein;
DE AltName: Full=Pr125Pol;
DE Contains:
DE RecName: Full=Protease/Reverse transcriptase/ribonuclease H;
DE EC=2.7.7.49;
DE EC=2.7.7.7;
DE EC=3.1.26.4;
DE EC=3.4.23.-;
DE AltName: Full=p87Pro-RT-RNaseH;
DE Contains:
DE RecName: Full=Protease/Reverse transcriptase;
DE EC=2.7.7.49;
DE EC=2.7.7.7;
DE EC=3.4.23.-;
DE AltName: Full=p65Pro-RT;
DE Contains:
DE RecName: Full=Ribonuclease H;
DE Short=RNase H;
DE EC=3.1.26.4;
DE Contains:
DE RecName: Full=Integrase;
DE Short=IN;
DE EC=2.7.7.- {ECO:0000305|PubMed:23872492};
DE EC=3.1.-.- {ECO:0000305|PubMed:23872492};
DE AltName: Full=p42In;
GN Name=pol;
OS Human spumaretrovirus (SFVcpz(hu)) (Human foamy virus).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Spumaretrovirinae; Spumavirus.
OX NCBI_TaxID=11963;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND SEQUENCE REVISION.
RA Fluegel R.M.;
RL Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Schmidt M., Herchenrder O., Heeney J.L., Rethwilm A.;
RT "Long terminal repeat U3-length polymorphism of human foamy virus.";
RL Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-742.
RX PubMed=2451755; DOI=10.1128/jvi.62.5.1590-1597.1988;
RA Maurer B., Bannert H., Darai G., Fluegel R.M.;
RT "Analysis of the primary structure of the long terminal repeat and the gag
RT and pol genes of the human spumaretrovirus.";
RL J. Virol. 62:1590-1597(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 741-886.
RX PubMed=2820721; DOI=10.1002/j.1460-2075.1987.tb02473.x;
RA Fluegel R.M., Rethwilm A., Maurer B., Darai G.;
RT "Nucleotide sequence analysis of the env gene and its flanking regions of
RT the human spumaretrovirus reveals two novel genes.";
RL EMBO J. 6:2077-2084(1987).
RN [5]
RP ACTIVE SITE OF PROTEASE, AND MUTAGENESIS OF ASP-24 AND SER-25.
RX PubMed=7474150; DOI=10.1128/jvi.69.11.7264-7268.1995;
RA Konvalinka J., Loechelt M., Zentgraf H., Fluegel R.M., Kraeusslich H.-G.;
RT "Active foamy virus proteinase is essential for virus infectivity but not
RT for formation of a Pol polyprotein.";
RL J. Virol. 69:7264-7268(1995).
RN [6]
RP MUTAGENESIS OF PRO-152; PRO-169; PRO-193; ASP-599 AND TYR-672.
RX PubMed=7544460; DOI=10.1093/nar/23.14.2621;
RA Kogel D., Aboud M., Fluegel R.M.;
RT "Mutational analysis of the reverse transcriptase and ribonuclease H
RT domains of the human foamy virus.";
RL Nucleic Acids Res. 23:2621-2625(1995).
RN [7]
RP CHARACTERIZATION OF POLYPROTEIN.
RX PubMed=8551561; DOI=10.1128/jvi.70.2.1033-1040.1996;
RA Loechelt M., Fluegel R.M.;
RT "The human foamy virus pol gene is expressed as a Pro-Pol polyprotein and
RT not as a Gag-Pol fusion protein.";
RL J. Virol. 70:1033-1040(1996).
RN [8]
RP PROTEOLYTIC PROCESSING OF POLYPROTEIN.
RX PubMed=9696869; DOI=10.1128/jvi.72.9.7648-7652.1998;
RA Pfrepper K.-I., Rackwitz H.R., Schnoelzer M., Heid H., Loechelt M.,
RA Fluegel R.M.;
RT "Molecular characterization of proteolytic processing of the Pol proteins
RT of human foamy virus reveals novel features of the viral protease.";
RL J. Virol. 72:7648-7652(1998).
RN [9]
RP SUBCELLULAR LOCATION.
RC STRAIN=Isolate HSRV2;
RX PubMed=11086125; DOI=10.1099/0022-1317-81-12-2941;
RA Imrich H., Heinkelein M., Herchenroder O., Rethwilm A.;
RT "Primate foamy virus Pol proteins are imported into the nucleus.";
RL J. Gen. Virol. 81:2941-2947(2000).
RN [10]
RP CHARACTERIZATION OF REVERSE TRANSCRIPTASE.
RX PubMed=12829852; DOI=10.1128/jvi.77.14.8141-8146.2003;
RA Delelis O., Saib A., Sonigo P.;
RT "Biphasic DNA synthesis in spumaviruses.";
RL J. Virol. 77:8141-8146(2003).
RN [11]
RP CHARACTERIZATION OF INTEGRASE.
RX PubMed=14963145; DOI=10.1128/jvi.78.5.2472-2477.2004;
RA Juretzek T., Holm T., Gartner K., Kanzler S., Lindemann D.,
RA Herchenroder O., Picard-Maureau M., Rammling M., Heinkelein M.,
RA Rethwilm A.;
RT "Foamy virus integration.";
RL J. Virol. 78:2472-2477(2004).
RN [12]
RP REVIEW.
RX PubMed=12908768; DOI=10.1007/978-3-642-55701-9_3;
RA Fluegel R.M., Pfrepper K.-I.;
RT "Proteolytic processing of foamy virus Gag and Pol proteins.";
RL Curr. Top. Microbiol. Immunol. 277:63-88(2003).
RN [13]
RP REVIEW.
RX PubMed=15358259; DOI=10.1016/j.mib.2004.06.009;
RA Delelis O., Lehmann-Che J., Saib A.;
RT "Foamy viruses-a world apart.";
RL Curr. Opin. Microbiol. 7:400-406(2004).
RN [14]
RP REVIEW (INTEGRASE).
RX PubMed=23872492; DOI=10.3390/v5071850;
RA Hossain M.A., Ali M.K., Shin C.G.;
RT "Structural and functional insights into foamy viral integrase.";
RL Viruses 5:1850-1866(2013).
CC -!- FUNCTION: The aspartyl protease activity mediates proteolytic cleavages
CC of Gag and Pol polyproteins. The reverse transcriptase (RT) activity
CC converts the viral RNA genome into dsDNA in the cytoplasm, shortly
CC after virus entry into the cell (early reverse transcription) or after
CC proviral DNA transcription (late reverse transcription). RT consists of
CC a DNA polymerase activity that can copy either DNA or RNA templates,
CC and a ribonuclease H (RNase H) activity that cleaves the RNA strand of
CC RNA-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-Lys1,2 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 a
CC polypurine tract (PPT) 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 PPT that has not been removed by RNase H as
CC primer. PPT and tRNA primers are then removed by RNase H. The 3' and 5'
CC 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 (By 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 at least the viral genome, matrix protein, and
CC integrase. This complex is called the pre-integration complex (PIC).
CC The integrase protein removes 2 nucleotides from the 3' end of the
CC viral DNA right (U5) end, leaving the left (U3) intact. In the second
CC step, the PIC enters cell nucleus. This process is mediated through the
CC integrase and allows the virus to infect both dividing (nuclear
CC membrane disassembled) and G1/S-arrested cells (active translocation),
CC but with no viral gene expression in the latter. In the third step,
CC termed strand transfer, the integrase protein joins the previously
CC processed 3' ends to the 5' ends of strands of target cellular DNA at
CC the site of integration. It is however not clear how integration then
CC proceeds to resolve the asymmetrical cleavage of viral DNA (By
CC similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.4;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00408};
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 -!- SUBUNIT: The protease is a homodimer, whose active site consists of two
CC apposed aspartic acid residues. {ECO:0000255|PROSITE-ProRule:PRU00863}.
CC -!- INTERACTION:
CC PRO_0000245446; PRO_0000245446 [P14350]: pol; NbExp=6; IntAct=EBI-16013918, EBI-16013918;
CC -!- SUBCELLULAR LOCATION: [Integrase]: Virion {ECO:0000305}. Host nucleus.
CC Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase,
CC cytoplasmic at assembly. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Protease/Reverse transcriptase/ribonuclease H]:
CC Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000305}. Note=Nuclear
CC at initial phase, cytoplasmic at assembly. {ECO:0000305}.
CC -!- DOMAIN: The 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 (By similarity). {ECO:0000250}.
CC -!- DOMAIN: Integrase core domain contains the D-x(n)-D-x(35)-E motif,
CC named for the phylogenetically conserved glutamic acid and aspartic
CC acid residues and the invariant 35 amino acid spacing between the
CC second and third acidic residues. Each acidic residue of the D,D(35)E
CC motif is independently essential for the 3'-processing and strand
CC transfer activities of purified integrase protein (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Specific enzymatic cleavages in vivo by viral protease yield
CC mature proteins. The protease is not cleaved off from Pol. Since
CC cleavage efficiency is not optimal for all sites, long and active
CC p65Pro-RT, p87Pro-RT-RNaseH and even some Pr125Pol are detected in
CC infected cells. {ECO:0000269|PubMed:9696869}.
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: Foamy viruses are distinct from other retroviruses in
CC many respects. Their protease is active as an uncleaved Pro-Pol
CC protein. Mature particles do not include the usual processed retroviral
CC structural protein (MA, CA and NC), but instead contain two large Gag
CC proteins. Their functional nucleic acid appears to be either RNA or
CC dsDNA (up to 20% of extracellular particles), because they probably
CC proceed either to an early (before integration) or late reverse
CC transcription (after assembly). Foamy viruses have the ability to
CC retrotranspose intracellularly with high efficiency. They bud
CC predominantly into the endoplasmic reticulum (ER) and occasionally at
CC the plasma membrane. Budding requires the presence of Env proteins.
CC Most viral particles probably remain within the infected cell.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA46122.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAA66556.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U21247; AAB48112.1; -; Genomic_RNA.
DR EMBL; Y07723; CAA68997.1; -; Genomic_DNA.
DR EMBL; Y07724; CAA68999.1; -; Genomic_DNA.
DR EMBL; Y07725; CAA69003.1; -; Genomic_DNA.
DR EMBL; M19427; AAA66556.1; ALT_INIT; Genomic_RNA.
DR EMBL; M54978; AAA46122.1; ALT_FRAME; Genomic_RNA.
DR PDB; 2LSN; NMR; -; A=591-751.
DR PDB; 2X6N; X-ray; 2.06 A; A/B/C/D/E/F=861-1060.
DR PDB; 2X6S; X-ray; 2.29 A; A/B/C/D/E/F=861-1060.
DR PDB; 2X74; X-ray; 2.34 A; A/B/C/D/E/F=861-1060.
DR PDB; 2X78; X-ray; 2.00 A; A/B/C=861-1060.
DR PDB; 3DLR; X-ray; 2.20 A; A=859-1058.
DR PDB; 3L2Q; X-ray; 3.25 A; A/B=752-1143.
DR PDB; 3L2R; X-ray; 2.88 A; A/B=752-1143.
DR PDB; 3L2U; X-ray; 3.15 A; A/B=752-1143.
DR PDB; 3L2V; X-ray; 3.20 A; A/B=752-1143.
DR PDB; 3L2W; X-ray; 3.20 A; A/B=752-1143.
DR PDB; 3OS0; X-ray; 2.81 A; A/B=752-1143.
DR PDB; 3OS1; X-ray; 2.97 A; A/B=752-1143.
DR PDB; 3OS2; X-ray; 3.32 A; A/B=752-1143.
DR PDB; 3OY9; X-ray; 2.95 A; A/B=752-1143.
DR PDB; 3OYA; X-ray; 2.85 A; A/B=752-1143.
DR PDB; 3OYB; X-ray; 2.54 A; A/B=752-1143.
DR PDB; 3OYC; X-ray; 2.66 A; A/B=752-1143.
DR PDB; 3OYD; X-ray; 2.54 A; A/B=752-1143.
DR PDB; 3OYE; X-ray; 2.74 A; A/B=752-1143.
DR PDB; 3OYF; X-ray; 2.51 A; A/B=752-1143.
DR PDB; 3OYG; X-ray; 2.56 A; A/B=752-1143.
DR PDB; 3OYH; X-ray; 2.74 A; A/B=752-1143.
DR PDB; 3OYI; X-ray; 2.72 A; A/B=752-1143.
DR PDB; 3OYJ; X-ray; 2.68 A; A/B=752-1143.
DR PDB; 3OYK; X-ray; 2.72 A; A/B=752-1143.
DR PDB; 3OYL; X-ray; 2.54 A; A/B=752-1143.
DR PDB; 3OYM; X-ray; 2.02 A; A/B=752-1143.
DR PDB; 3OYN; X-ray; 2.68 A; A/B=752-1143.
DR PDB; 3S3M; X-ray; 2.49 A; A/B=752-1143.
DR PDB; 3S3N; X-ray; 2.49 A; A/B=752-1143.
DR PDB; 3S3O; X-ray; 2.55 A; A/B=752-1143.
DR PDB; 4BAC; X-ray; 3.26 A; A/B=752-1143.
DR PDB; 4BDY; X-ray; 2.52 A; A/B=752-1143.
DR PDB; 4BDZ; X-ray; 2.85 A; A/B=752-1143.
DR PDB; 4BE0; X-ray; 2.68 A; A/B=752-1143.
DR PDB; 4BE1; X-ray; 2.71 A; A/B=752-1143.
DR PDB; 4BE2; X-ray; 2.38 A; A/B=752-1143.
DR PDB; 4E7H; X-ray; 2.57 A; A/B=752-1143.
DR PDB; 4E7I; X-ray; 2.53 A; A/B=752-1143.
DR PDB; 4E7J; X-ray; 3.15 A; A/B=752-1143.
DR PDB; 4E7K; X-ray; 3.02 A; A/B=752-1143.
DR PDB; 4E7L; X-ray; 3.00 A; A/B=752-1143.
DR PDB; 4IKF; X-ray; 3.40 A; A/B=752-1143.
DR PDB; 4ZTF; X-ray; 2.70 A; A/B=752-1143.
DR PDB; 4ZTJ; X-ray; 2.67 A; A/B=752-1143.
DR PDB; 5FRM; X-ray; 2.58 A; A/B=752-1143.
DR PDB; 5FRN; X-ray; 2.85 A; A/B=752-1143.
DR PDB; 5FRO; X-ray; 2.67 A; A/B=752-1143.
DR PDB; 5MMA; X-ray; 2.55 A; A/B=752-1143.
DR PDB; 5MMB; X-ray; 2.77 A; A/B=753-1143.
DR PDB; 5NO1; X-ray; 2.60 A; A/B=754-1143.
DR PDB; 5UOP; X-ray; 2.85 A; A/B=752-1143.
DR PDB; 5UOQ; X-ray; 2.61 A; A/B=752-1143.
DR PDB; 6RNY; EM; 3.90 A; K/L/O/P=754-1143.
DR PDB; 7ADU; X-ray; 2.62 A; A/B=754-1143.
DR PDB; 7ADV; X-ray; 2.65 A; A/B=754-1143.
DR PDBsum; 2LSN; -.
DR PDBsum; 2X6N; -.
DR PDBsum; 2X6S; -.
DR PDBsum; 2X74; -.
DR PDBsum; 2X78; -.
DR PDBsum; 3DLR; -.
DR PDBsum; 3L2Q; -.
DR PDBsum; 3L2R; -.
DR PDBsum; 3L2U; -.
DR PDBsum; 3L2V; -.
DR PDBsum; 3L2W; -.
DR PDBsum; 3OS0; -.
DR PDBsum; 3OS1; -.
DR PDBsum; 3OS2; -.
DR PDBsum; 3OY9; -.
DR PDBsum; 3OYA; -.
DR PDBsum; 3OYB; -.
DR PDBsum; 3OYC; -.
DR PDBsum; 3OYD; -.
DR PDBsum; 3OYE; -.
DR PDBsum; 3OYF; -.
DR PDBsum; 3OYG; -.
DR PDBsum; 3OYH; -.
DR PDBsum; 3OYI; -.
DR PDBsum; 3OYJ; -.
DR PDBsum; 3OYK; -.
DR PDBsum; 3OYL; -.
DR PDBsum; 3OYM; -.
DR PDBsum; 3OYN; -.
DR PDBsum; 3S3M; -.
DR PDBsum; 3S3N; -.
DR PDBsum; 3S3O; -.
DR PDBsum; 4BAC; -.
DR PDBsum; 4BDY; -.
DR PDBsum; 4BDZ; -.
DR PDBsum; 4BE0; -.
DR PDBsum; 4BE1; -.
DR PDBsum; 4BE2; -.
DR PDBsum; 4E7H; -.
DR PDBsum; 4E7I; -.
DR PDBsum; 4E7J; -.
DR PDBsum; 4E7K; -.
DR PDBsum; 4E7L; -.
DR PDBsum; 4IKF; -.
DR PDBsum; 4ZTF; -.
DR PDBsum; 4ZTJ; -.
DR PDBsum; 5FRM; -.
DR PDBsum; 5FRN; -.
DR PDBsum; 5FRO; -.
DR PDBsum; 5MMA; -.
DR PDBsum; 5MMB; -.
DR PDBsum; 5NO1; -.
DR PDBsum; 5UOP; -.
DR PDBsum; 5UOQ; -.
DR PDBsum; 6RNY; -.
DR PDBsum; 7ADU; -.
DR PDBsum; 7ADV; -.
DR SMR; P14350; -.
DR DIP; DIP-58582N; -.
DR MEROPS; A09.001; -.
DR PRIDE; P14350; -.
DR BRENDA; 3.1.13.2; 2705.
DR EvolutionaryTrace; P14350; -.
DR Proteomes; UP000138352; Genome.
DR Proteomes; UP000165559; 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:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion 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:UniProtKB-EC.
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: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 Gene3D; 2.40.70.10; -; 1.
DR Gene3D; 3.30.420.10; -; 2.
DR Gene3D; 3.30.70.270; -; 2.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR001584; Integrase_cat-core.
DR InterPro; IPR041588; Integrase_H2C2.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
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; IPR041577; RT_RNaseH_2.
DR InterPro; IPR040903; SH3_11.
DR InterPro; IPR001641; Spumavirus_A9.
DR Pfam; PF17921; Integrase_H2C2; 1.
DR Pfam; PF00075; RNase_H; 1.
DR Pfam; PF17919; RT_RNaseH_2; 1.
DR Pfam; PF00665; rve; 1.
DR Pfam; PF00078; RVT_1; 1.
DR Pfam; PF18103; SH3_11; 1.
DR Pfam; PF03539; Spuma_A9PTase; 1.
DR PRINTS; PR00920; SPUMVIRPTASE.
DR SUPFAM; SSF53098; SSF53098; 2.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS51531; FV_PR; 1.
DR PROSITE; PS50994; INTEGRASE; 1.
DR PROSITE; PS50879; RNASE_H_1; 1.
DR PROSITE; PS50878; RT_POL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aspartyl protease; DNA integration; DNA recombination;
KW DNA-directed DNA polymerase; Endonuclease; Host cytoplasm; Host nucleus;
KW Hydrolase; Magnesium; Metal-binding; Multifunctional enzyme; Nuclease;
KW Nucleotidyltransferase; Protease; Reference proteome; RNA-binding;
KW RNA-directed DNA polymerase; Transferase; Viral genome integration;
KW Viral penetration into host nucleus; Virion; Virus entry into host cell.
FT CHAIN 1..1143
FT /note="Pro-Pol polyprotein"
FT /id="PRO_0000125483"
FT CHAIN 1..751
FT /note="Protease/Reverse transcriptase/ribonuclease H"
FT /id="PRO_0000245443"
FT CHAIN 1..596
FT /note="Protease/Reverse transcriptase"
FT /id="PRO_0000245444"
FT CHAIN 597..751
FT /note="Ribonuclease H"
FT /id="PRO_0000245445"
FT CHAIN 752..1143
FT /note="Integrase"
FT /id="PRO_0000245446"
FT DOMAIN 1..143
FT /note="Peptidase A9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00863"
FT DOMAIN 198..363
FT /note="Reverse transcriptase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT DOMAIN 590..748
FT /note="RNase H type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT DOMAIN 868..1024
FT /note="Integrase catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00457"
FT REGION 1117..1143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1117..1135
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 24
FT /note="For protease activity"
FT /evidence="ECO:0000305|PubMed:7474150"
FT BINDING 252
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 314
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 315
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 599
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:0000305"
FT BINDING 646
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 669
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 740
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 874
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 936
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 596..597
FT /note="Cleavage; by viral protease; partial"
FT SITE 751..752
FT /note="Cleavage; by viral protease"
FT MUTAGEN 24
FT /note="D->A: Complete loss of Gag processing and of Pol
FT processing. Particles are non-infectious."
FT /evidence="ECO:0000269|PubMed:7474150"
FT MUTAGEN 25
FT /note="S->T: No effect on polyprotein processing and viral
FT replication."
FT /evidence="ECO:0000269|PubMed:7474150"
FT MUTAGEN 152
FT /note="P->G: No effect on RT or RNase H activities."
FT /evidence="ECO:0000269|PubMed:7544460"
FT MUTAGEN 169
FT /note="P->G: 30% loss of RT activity."
FT /evidence="ECO:0000269|PubMed:7544460"
FT MUTAGEN 193
FT /note="P->G: 40% loss of RT activity."
FT /evidence="ECO:0000269|PubMed:7544460"
FT MUTAGEN 599
FT /note="D->A: 95% loss of RNase H activity."
FT /evidence="ECO:0000269|PubMed:7544460"
FT MUTAGEN 672
FT /note="Y->F: 50% loss of RNase H activity."
FT /evidence="ECO:0000269|PubMed:7544460"
FT STRAND 593..603
FT /evidence="ECO:0007829|PDB:2LSN"
FT STRAND 613..621
FT /evidence="ECO:0007829|PDB:2LSN"
FT STRAND 624..626
FT /evidence="ECO:0007829|PDB:2LSN"
FT STRAND 629..639
FT /evidence="ECO:0007829|PDB:2LSN"
FT HELIX 642..659
FT /evidence="ECO:0007829|PDB:2LSN"
FT STRAND 660..662
FT /evidence="ECO:0007829|PDB:2LSN"
FT STRAND 664..669
FT /evidence="ECO:0007829|PDB:2LSN"
FT HELIX 671..678
FT /evidence="ECO:0007829|PDB:2LSN"
FT HELIX 680..686
FT /evidence="ECO:0007829|PDB:2LSN"
FT STRAND 693..695
FT /evidence="ECO:0007829|PDB:2LSN"
FT HELIX 700..712
FT /evidence="ECO:0007829|PDB:2LSN"
FT STRAND 717..720
FT /evidence="ECO:0007829|PDB:2LSN"
FT STRAND 723..725
FT /evidence="ECO:0007829|PDB:2LSN"
FT STRAND 727..729
FT /evidence="ECO:0007829|PDB:2LSN"
FT HELIX 731..749
FT /evidence="ECO:0007829|PDB:2LSN"
FT HELIX 760..767
FT /evidence="ECO:0007829|PDB:3OYM"
FT STRAND 773..775
FT /evidence="ECO:0007829|PDB:3L2V"
FT STRAND 777..779
FT /evidence="ECO:0007829|PDB:3L2R"
FT STRAND 781..784
FT /evidence="ECO:0007829|PDB:3OYM"
FT STRAND 787..792
FT /evidence="ECO:0007829|PDB:3OYM"
FT STRAND 795..798
FT /evidence="ECO:0007829|PDB:3OYM"
FT HELIX 802..804
FT /evidence="ECO:0007829|PDB:3OYM"
FT HELIX 805..814
FT /evidence="ECO:0007829|PDB:3OYM"
FT TURN 815..817
FT /evidence="ECO:0007829|PDB:3OYM"
FT HELIX 820..828
FT /evidence="ECO:0007829|PDB:3OYM"
FT HELIX 836..844
FT /evidence="ECO:0007829|PDB:3OYM"
FT HELIX 848..853
FT /evidence="ECO:0007829|PDB:3OYM"
FT STRAND 858..860
FT /evidence="ECO:0007829|PDB:3OYM"
FT STRAND 874..881
FT /evidence="ECO:0007829|PDB:2X78"
FT STRAND 892..898
FT /evidence="ECO:0007829|PDB:2X78"
FT TURN 899..901
FT /evidence="ECO:0007829|PDB:2X78"
FT STRAND 904..912
FT /evidence="ECO:0007829|PDB:2X78"
FT HELIX 914..924
FT /evidence="ECO:0007829|PDB:2X78"
FT TURN 925..927
FT /evidence="ECO:0007829|PDB:2X78"
FT STRAND 931..935
FT /evidence="ECO:0007829|PDB:2X78"
FT HELIX 939..942
FT /evidence="ECO:0007829|PDB:2X78"
FT HELIX 944..953
FT /evidence="ECO:0007829|PDB:2X78"
FT STRAND 956..959
FT /evidence="ECO:0007829|PDB:2X78"
FT HELIX 965..968
FT /evidence="ECO:0007829|PDB:3OYM"
FT HELIX 970..987
FT /evidence="ECO:0007829|PDB:2X78"
FT TURN 990..996
FT /evidence="ECO:0007829|PDB:2X78"
FT HELIX 997..1005
FT /evidence="ECO:0007829|PDB:2X78"
FT TURN 1010..1012
FT /evidence="ECO:0007829|PDB:2X78"
FT HELIX 1016..1021
FT /evidence="ECO:0007829|PDB:2X78"
FT STRAND 1023..1025
FT /evidence="ECO:0007829|PDB:2X6N"
FT STRAND 1028..1030
FT /evidence="ECO:0007829|PDB:2X74"
FT TURN 1033..1036
FT /evidence="ECO:0007829|PDB:3OYM"
FT HELIX 1040..1054
FT /evidence="ECO:0007829|PDB:2X78"
FT STRAND 1073..1077
FT /evidence="ECO:0007829|PDB:3OYM"
FT STRAND 1092..1099
FT /evidence="ECO:0007829|PDB:3OYM"
FT STRAND 1102..1106
FT /evidence="ECO:0007829|PDB:3OYM"
FT STRAND 1108..1110
FT /evidence="ECO:0007829|PDB:4BE2"
FT STRAND 1112..1116
FT /evidence="ECO:0007829|PDB:3OYM"
FT HELIX 1117..1119
FT /evidence="ECO:0007829|PDB:3OYM"
FT STRAND 1120..1122
FT /evidence="ECO:0007829|PDB:3OYM"
SQ SEQUENCE 1143 AA; 129742 MW; 786E3203B06FFB3C CRC64;
MNPLQLLQPL PAEIKGTKLL AHWDSGATIT CIPESFLEDE QPIKKTLIKT IHGEKQQNVY
YVTFKVKGRK VEAEVIASPY EYILLSPTDV PWLTQQPLQL TILVPLQEYQ EKILSKTALP
EDQKQQLKTL FVKYDNLWQH WENQVGHRKI RPHNIATGDY PPRPQKQYPI NPKAKPSIQI
VIDDLLKQGV LTPQNSTMNT PVYPVPKPDG RWRMVLDYRE VNKTIPLTAA QNQHSAGILA
TIVRQKYKTT LDLANGFWAH PITPESYWLT AFTWQGKQYC WTRLPQGFLN SPALFTADVV
DLLKEIPNVQ VYVDDIYLSH DDPKEHVQQL EKVFQILLQA GYVVSLKKSE IGQKTVEFLG
FNITKEGRGL TDTFKTKLLN ITPPKDLKQL QSILGLLNFA RNFIPNFAEL VQPLYNLIAS
AKGKYIEWSE ENTKQLNMVI EALNTASNLE ERLPEQRLVI KVNTSPSAGY VRYYNETGKK
PIMYLNYVFS KAELKFSMLE KLLTTMHKAL IKAMDLAMGQ EILVYSPIVS MTKIQKTPLP
ERKALPIRWI TWMTYLEDPR IQFHYDKTLP ELKHIPDVYT SSQSPVKHPS QYEGVFYTDG
SAIKSPDPTK SNNAGMGIVH ATYKPEYQVL NQWSIPLGNH TAQMAEIAAV EFACKKALKI
PGPVLVITDS FYVAESANKE LPYWKSNGFV NNKKKPLKHI SKWKSIAECL SMKPDITIQH
EKGISLQIPV FILKGNALAD KLATQGSYVV NCNTKKPNLD AELDQLLQGH YIKGYPKQYT
YFLEDGKVKV SRPEGVKIIP PQSDRQKIVL QAHNLAHTGR EATLLKIANL YWWPNMRKDV
VKQLGRCQQC LITNASNKAS GPILRPDRPQ KPFDKFFIDY IGPLPPSQGY LYVLVVVDGM
TGFTWLYPTK APSTSATVKS LNVLTSIAIP KVIHSDQGAA FTSSTFAEWA KERGIHLEFS
TPYHPQSGSK VERKNSDIKR LLTKLLVGRP TKWYDLLPVV QLALNNTYSP VLKYTPHQLL
FGIDSNTPFA NQDTLDLTRE EELSLLQEIR TSLYHPSTPP ASSRSWSPVV GQLVQERVAR
PASLRPRWHK PSTVLKVLNP RTVVILDHLG NNRTVSIDNL KPTSHQNGTT NDTATMDHLE
KNE
