ID   POL_HTL1A               Reviewed;        1462 AA.
AC   P03362; Q85590;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   04-NOV-2026, entry version 178.
DE   RecName: Full=Gag-Pro-Pol polyprotein;
DE   AltName: Full=Pr160Gag-Pro-Pol;
DE   Contains:
DE     RecName: Full=Matrix protein p19;
DE              Short=MA;
DE   Contains:
DE     RecName: Full=Capsid protein p24;
DE              Short=CA;
DE   Contains:
DE     RecName: Full=Nucleocapsid protein p15-pro;
DE              Short=NC';
DE              Short=NC-pro;
DE   Contains:
DE     RecName: Full=Protease;
DE              Short=PR;
DE              EC=3.4.23.- {ECO:0000255|PROSITE-ProRule:PRU00275, ECO:0000269|PubMed:15102858};
DE   Contains:
DE     RecName: Full=p1;
DE   Contains:
DE     RecName: Full=Reverse transcriptase/ribonuclease H, p49 subunit;
DE              Short=p49 RT;
DE              EC=2.7.7.49 {ECO:0000255|PROSITE-ProRule:PRU00405};
DE              EC=2.7.7.7 {ECO:0000255|PROSITE-ProRule:PRU00405};
DE              EC=3.1.26.4 {ECO:0000255|PROSITE-ProRule:PRU00408};
DE   Contains:
DE     RecName: Full=Reverse transcriptase/ribonuclease H, p62 subunit;
DE              Short=p62 RT;
DE              EC=2.7.7.49 {ECO:0000255|PROSITE-ProRule:PRU00405};
DE              EC=2.7.7.7 {ECO:0000255|PROSITE-ProRule:PRU00405};
DE              EC=3.1.26.4 {ECO:0000255|PROSITE-ProRule:PRU00408};
DE   Contains:
DE     RecName: Full=Integrase;
DE              Short=IN;
DE              EC=2.7.7.- {ECO:0000250|UniProtKB:P03363};
DE              EC=3.1.-.- {ECO:0000250|UniProtKB:P03363};
GN   Name=gag-pro-pol;
OS   Human T-cell leukemia virus 1 (strain Japan ATK-1 subtype A) (HTLV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Deltaretrovirus;
OC   Deltaretrovirus priTlym1; Primate T-lymphotropic virus 1.
OX   NCBI_TaxID=11926;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6304725; DOI=10.1073/pnas.80.12.3618;
RA   Seiki M., Hattori S., Hirayama Y., Yoshida M.C.;
RT   "Human adult T-cell leukemia virus: complete nucleotide sequence of the
RT   provirus genome integrated in leukemia cell DNA.";
RL   Proc. Natl. Acad. Sci. U.S.A. 80:3618-3622(1983).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 395-672.
RX   PubMed=3021121; DOI=10.1016/s0006-291x(86)80089-4;
RA   Nam S.H., Hatanaka M.;
RT   "Identification of a protease gene of human T-cell leukemia virus type I
RT   (HTLV-I) and its structural comparison.";
RL   Biochem. Biophys. Res. Commun. 139:129-135(1986).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 635-751.
RX   PubMed=2468487; DOI=10.1002/j.1460-2075.1988.tb03314.x;
RA   Bangham C.R.M., Daenke S., Philips R.E., Cruickshank J.K., Bell J.I.;
RT   "Enzymatic amplification of exogenous and endogenous retroviral sequences
RT   from DNA of patients with tropical spastic paraparesis.";
RL   EMBO J. 7:4179-4184(1988).
RN   [4]
RP   PROTEIN SEQUENCE OF 131-155.
RX   PubMed=6280175; DOI=10.1073/pnas.79.4.1291;
RA   Oroszlan S., Sarngadharan M.G., Copeland T.D., Kalyanaraman V.S.,
RA   Gilden R.V., Gallo R.C.;
RT   "Primary structure analysis of the major internal protein p24 of human type
RT   C T-cell leukemia virus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 79:1291-1294(1982).
RN   [5]
RP   PROTEIN SEQUENCE OF 545-611, AND PROTEOLYTIC CLEAVAGE (GAG-PRO-POL
RP   POLYPROTEIN).
RX   PubMed=11469799; DOI=10.1006/abbi.2001.2432;
RA   Agbuya P.G., Sherman N.E., Moen L.K.;
RT   "Proteolytic processing of the human T-cell lymphotropic virus 1 reverse
RT   transcriptase: identification of the N-terminal cleavage site by mass
RT   spectrometry.";
RL   Arch. Biochem. Biophys. 392:93-102(2001).
RN   [6]
RP   PROTEIN SEQUENCE OF 596-612, AND RIBOSOMAL FRAMESHIFT.
RX   PubMed=8416368; DOI=10.1128/jvi.67.1.196-203.1993;
RA   Nam S.H., Copeland T.D., Hatanaka M., Oroszlan S.;
RT   "Characterization of ribosomal frameshifting for expression of pol gene
RT   products of human T-cell leukemia virus type I.";
RL   J. Virol. 67:196-203(1993).
RN   [7]
RP   FUNCTION (PROTEASE).
RX   PubMed=2843670; DOI=10.1128/jvi.62.10.3718-3728.1988;
RA   Nam S.H., Kidokoro M., Shida H., Hatanaka M.;
RT   "Processing of gag precursor polyprotein of human T-cell leukemia virus
RT   type I by virus-encoded protease.";
RL   J. Virol. 62:3718-3728(1988).
RN   [8]
RP   CHARACTERIZATION (PROTEASE), AND PROTEOLYTIC CLEAVAGE (GAG-PRO-POL
RP   POLYPROTEIN).
RX   PubMed=10037763; DOI=10.1074/jbc.274.10.6660;
RA   Louis J.M., Oroszlan S., Toezser J.;
RT   "Stabilization from autoproteolysis and kinetic characterization of the
RT   human T-cell leukemia virus type 1 proteinase.";
RL   J. Biol. Chem. 274:6660-6666(1999).
RN   [9]
RP   DOMAIN (CAPSID PROTEIN P24), MUTAGENESIS OF GLY-2, AND MYRISTOYLATION AT
RP   GLY-2.
RX   PubMed=11333909; DOI=10.1128/jvi.75.11.5277-5287.2001;
RA   Rayne F., Bouamr F., Lalanne J., Mamoun R.Z.;
RT   "The NH2-terminal domain of the human T-cell leukemia virus type 1 capsid
RT   protein is involved in particle formation.";
RL   J. Virol. 75:5277-5287(2001).
RN   [10]
RP   REVIEW (PROTEASE).
RX   PubMed=12770819; DOI=10.1016/s1074-5521(03)00104-2;
RA   Shuker S.B., Mariani V.L., Herger B.E., Dennison K.J.;
RT   "Understanding HTLV-I protease.";
RL   Chem. Biol. 10:373-380(2003).
RN   [11]
RP   FUNCTION (PROTEASE).
RX   PubMed=14610163; DOI=10.1128/jvi.77.23.12392-12400.2003;
RA   Alvarez E., Menendez-Arias L., Carrasco L.;
RT   "The eukaryotic translation initiation factor 4GI is cleaved by different
RT   retroviral proteases.";
RL   J. Virol. 77:12392-12400(2003).
RN   [12]
RP   PROTEOLYTIC CLEAVAGE (GAG-PRO-POL POLYPROTEIN).
RX   PubMed=12504078; DOI=10.1016/s0006-291x(02)02848-6;
RA   Mariani V.L., Shuker S.B.;
RT   "Identification of the RT-RH/IN cleavage site of HTLV-I.";
RL   Biochem. Biophys. Res. Commun. 300:268-270(2003).
RN   [13]
RP   CHARACTERIZATION (PROTEASE), FUNCTION (PROTEASE), CATALYTIC ACTIVITY
RP   (PROTEASE), MUTAGENESIS OF MET-486; LEU-506; ALA-508; PHE-516; ASN-545;
RP   ASN-546 AND TRP-547, AND PROTEOLYTIC CLEAVAGE (GAG-PRO-POL POLYPROTEIN).
RX   PubMed=15102858; DOI=10.1074/jbc.m401868200;
RA   Kadas J., Weber I.T., Bagossi P., Miklossy G., Boross P., Oroszlan S.,
RA   Toezser J.;
RT   "Narrow substrate specificity and sensitivity toward ligand-binding site
RT   mutations of human T-cell Leukemia virus type 1 protease.";
RL   J. Biol. Chem. 279:27148-27157(2004).
RN   [14]
RP   PROTEOLYTIC CLEAVAGE (GAG-PRO-POL POLYPROTEIN).
RX   PubMed=16682197; DOI=10.1016/j.bmcl.2006.04.056;
RA   Naka H., Teruya K., Bang J.K., Aimoto S., Tatsumi T., Konno H., Nosaka K.,
RA   Akaji K.;
RT   "Evaluations of substrate specificity and inhibition at PR/p3 cleavage site
RT   of HTLV-1 protease.";
RL   Bioorg. Med. Chem. Lett. 16:3761-3764(2006).
RN   [15]
RP   PROTEOLYTIC CLEAVAGE (GAG-PRO-POL POLYPROTEIN).
RX   PubMed=16368688; DOI=10.1074/jbc.m507660200;
RA   Mitchell M.S., Toezser J., Princler G., Lloyd P.A., Auth A., Derse D.;
RT   "Synthesis, processing, and composition of the virion-associated HTLV-1
RT   reverse transcriptase.";
RL   J. Biol. Chem. 281:3964-3971(2006).
CC   -!- FUNCTION: [Gag-Pro-Pol polyprotein]: The matrix domain targets Gag,
CC       Gag-Pro and Gag-Pro-Pol polyproteins to the plasma membrane via a
CC       multipartite membrane binding signal, that includes its myristoylated
CC       N-terminus. {ECO:0000250|UniProtKB:P03345}.
CC   -!- FUNCTION: [Matrix protein p19]: Matrix protein.
CC       {ECO:0000250|UniProtKB:P03345}.
CC   -!- FUNCTION: [Capsid protein p24]: Forms the spherical core of the virus
CC       that encapsulates the genomic RNA-nucleocapsid complex. {ECO:0000305}.
CC   -!- FUNCTION: [Nucleocapsid protein p15-pro]: Binds strongly to viral
CC       nucleic acids and promote their aggregation. Also destabilizes the
CC       nucleic acids duplexes via highly structured zinc-binding motifs.
CC       {ECO:0000250|UniProtKB:P03345}.
CC   -!- FUNCTION: [Protease]: The aspartyl protease 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. Cleaves the translation
CC       initiation factor eIF4G leading to the inhibition of host cap-dependent
CC       translation (PubMed:14610163). {ECO:0000255|PROSITE-ProRule:PRU00275,
CC       ECO:0000269|PubMed:14610163, ECO:0000269|PubMed:15102858,
CC       ECO:0000269|PubMed:2843670}.
CC   -!- FUNCTION: [Reverse transcriptase/ribonuclease H, p49 subunit]: RT is a
CC       multifunctional enzyme that converts the viral RNA genome into dsDNA in
CC       the cytoplasm, shortly after virus entry into the cell. This enzyme
CC       displays a DNA polymerase activity that can copy either DNA or RNA
CC       templates, and a ribonuclease H (RNase H) activity that cleaves the RNA
CC       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-Pro binds to the primer-binding site (PBS) situated
CC       at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer
CC       to perform a short round of RNA-dependent minus-strand DNA synthesis.
CC       The reading proceeds through the U5 region and ends after the repeated
CC       (R) region which is present at both ends of viral RNA. The portion of
CC       the RNA-DNA heteroduplex is digested by the RNase H, resulting in a
CC       ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes
CC       with 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 a polypurine tract (PPT) situated at the 5' end of the
CC       genome. It is not clear if both polymerase and RNase H activities are
CC       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: [Reverse transcriptase/ribonuclease H, p62 subunit]: RT is a
CC       multifunctional enzyme that converts the viral RNA genome into dsDNA in
CC       the cytoplasm, shortly after virus entry into the cell. This enzyme
CC       displays a DNA polymerase activity that can copy either DNA or RNA
CC       templates, and a ribonuclease H (RNase H) activity that cleaves the RNA
CC       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-Pro binds to the primer-binding site (PBS) situated
CC       at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer
CC       to perform a short round of RNA-dependent minus-strand DNA synthesis.
CC       The reading proceeds through the U5 region and ends after the repeated
CC       (R) region which is present at both ends of viral RNA. The portion of
CC       the RNA-DNA heteroduplex is digested by the RNase H, resulting in a
CC       ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes
CC       with 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 a polypurine tract (PPT) situated at the 5' end of the
CC       genome. It is not clear if both polymerase and RNase H activities are
CC       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. {ECO:0000305}.
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=DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) +
CC         diphosphate; Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-
CC         COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112;
CC         EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) +
CC         diphosphate; Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-
CC         COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112;
CC         EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU00405};
CC       Note=The RT polymerase active site binds 2 magnesium ions.
CC       {ECO:0000255|PROSITE-ProRule:PRU00405};
CC   -!- SUBUNIT: [Gag-Pro-Pol polyprotein]: Homodimer; the homodimers are part
CC       of the immature particles. Interacts with human TSG101 and NEDD4; these
CC       interactions are essential for budding and release of viral particles.
CC       {ECO:0000250|UniProtKB:P03345}.
CC   -!- SUBUNIT: [Matrix protein p19]: Homodimer; further assembles as
CC       homohexamers. {ECO:0000250|UniProtKB:P03345}.
CC   -!- SUBCELLULAR LOCATION: [Matrix protein p19]: Virion
CC       {ECO:0000250|UniProtKB:P03345}.
CC   -!- SUBCELLULAR LOCATION: [Capsid protein p24]: Virion
CC       {ECO:0000250|UniProtKB:P03345}.
CC   -!- SUBCELLULAR LOCATION: [Nucleocapsid protein p15-pro]: Virion
CC       {ECO:0000250|UniProtKB:P03345}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Ribosomal frameshifting; Named isoforms=3;
CC         Comment=This strategy of translation probably allows the virus to
CC         modulate the quantity of each viral protein. {ECO:0000305};
CC       Name=Gag-Pro-Pol polyprotein;
CC         IsoId=P03362-1; Sequence=Displayed;
CC       Name=Gag-Pro polyprotein;
CC         IsoId=P10274-1; Sequence=External;
CC       Name=Gag polyprotein;
CC         IsoId=P03345-1; Sequence=External;
CC   -!- DOMAIN: Gag polyprotein: Late-budding domains (L domains) are short
CC       sequence motifs essential for viral particle release. They can occur
CC       individually or in close proximity within structural proteins. They
CC       interacts with sorting cellular proteins of the multivesicular body
CC       (MVB) pathway. Most of these proteins are class E vacuolar protein
CC       sorting factors belonging to ESCRT-I, ESCRT-II or ESCRT-III complexes.
CC       Matrix protein p19 contains two L domains: a PTAP/PSAP motif which
CC       interacts with the UEV domain of TSG101, and a PPXY motif which binds
CC       to the WW domains of the ubiquitin ligase NEDD4.
CC       {ECO:0000250|UniProtKB:P03345}.
CC   -!- DOMAIN: [Capsid protein p24]: The capsid protein N-terminus seems to be
CC       involved in Gag-Gag interactions. {ECO:0000269|PubMed:11333909}.
CC   -!- PTM: [Matrix protein p19]: Phosphorylation of the matrix protein p19 by
CC       MAPK1 seems to play a role in budding. {ECO:0000250|UniProtKB:P03345}.
CC   -!- PTM: [Gag-Pro-Pol polyprotein]: Myristoylated. Myristoylation of the
CC       matrix (MA) domain mediates the transport and binding of Gag
CC       polyproteins to the host plasma membrane and is required for the
CC       assembly of viral particles. {ECO:0000250|UniProtKB:P03345}.
CC   -!- PTM: [Gag-Pro-Pol polyprotein]: Specific enzymatic cleavages by the
CC       viral protease yield mature proteins. The polyprotein is cleaved during
CC       and after budding, this process is termed maturation. The protease is
CC       autoproteolytically processed at its N- and C-termini.
CC       {ECO:0000269|PubMed:10037763, ECO:0000269|PubMed:11469799,
CC       ECO:0000269|PubMed:12504078, ECO:0000269|PubMed:15102858,
CC       ECO:0000269|PubMed:16368688, ECO:0000269|PubMed:16682197}.
CC   -!- MISCELLANEOUS: Reverse transcriptase/ribonuclease H: The reverse
CC       transcriptase is an error-prone enzyme that lacks a proof-reading
CC       function. High mutations rate is a direct consequence of this
CC       characteristic. RT also displays frequent template switching leading to
CC       high recombination rate. Recombination mostly occurs between homologous
CC       regions of the two copackaged RNA genomes. If these two RNA molecules
CC       derive from different viral strains, reverse transcription will give
CC       rise to highly recombinated proviral DNAs. {ECO:0000255|PROSITE-
CC       ProRule:PRU00405}.
CC   -!- MISCELLANEOUS: HTLV-1 lineages are divided in four clades, A
CC       (Cosmopolitan), B (Central African group), C (Melanesian group) and D
CC       (New Central African group). {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform Gag-Pro-Pol polyprotein]: Produced by -1
CC       ribosomal frameshiftings at the gag-pro and gag-pol genes boundaries.
CC       {ECO:0000269|PubMed:8416368}.
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DR   EMBL; J02029; AAA96673.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; M13810; AAA46207.1; ALT_SEQ; Genomic_RNA.
DR   EMBL; X14144; CAA32360.1; -; Genomic_DNA.
DR   PIR; A03961; GNLJGH.
DR   PDB; 2B7F; X-ray; 2.60 A; A/B/C/D/E/F=450-565.
DR   PDB; 4YDG; X-ray; 3.25 A; A/B=450-565.
DR   BMRB; P03362; -.
DR   MDRepo; P03362; -.
DR   SMR; P03362; -.
DR   DrugCentral; P03362; -.
DR   iPTMnet; P03362; -.
DR   BRENDA; 3.4.23.B8; 2706.
DR   EvolutionaryTrace; P03362; -.
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: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:0005198; F:structural molecule activity; IEA:InterPro.
DR   GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW.
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:symbiont entry into host cell; IEA:UniProtKB-KW.
DR   GO; GO:0039657; P:symbiont-mediated suppression of host gene expression; IEA:UniProtKB-KW.
DR   GO; GO:0044826; P:viral genome integration into host DNA; IEA:UniProtKB-KW.
DR   GO; GO:0075523; P:viral translational frameshifting; IEA:UniProtKB-KW.
DR   FunFam; 1.10.185.10:FF:000001; Gag polyprotein; 1.
DR   Gene3D; 1.10.1200.30; -; 1.
DR   Gene3D; 3.30.70.270; -; 2.
DR   Gene3D; 2.40.70.10; Acid Proteases; 1.
DR   Gene3D; 1.10.185.10; Delta-retroviral matrix; 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; 3.30.420.10; Ribonuclease H-like superfamily/Ribonuclease H; 2.
DR   Gene3D; 4.10.60.10; Zinc finger, CCHC-type; 1.
DR   InterPro; IPR001969; Aspartic_peptidase_AS.
DR   InterPro; IPR003139; D_retro_matrix.
DR   InterPro; IPR043502; DNA/RNA_pol_sf.
DR   InterPro; IPR045345; Gag_p24_C.
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; IPR001995; Peptidase_A2_cat.
DR   InterPro; IPR021109; Peptidase_aspartic_dom_sf.
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; 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; PF02228; Gag_p19; 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; PF00098; zf-CCHC; 1.
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; 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; 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; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Aspartyl protease; Capsid protein; Direct protein sequencing;
KW   DNA integration; DNA recombination; DNA-binding;
KW   DNA-directed DNA polymerase; Endonuclease;
KW   Eukaryotic host gene expression shutoff by virus;
KW   Eukaryotic host translation shutoff by virus;
KW   Host gene expression shutoff by virus; Host-virus interaction; Hydrolase;
KW   Lipoprotein; Magnesium; Metal-binding; Multifunctional enzyme; Myristate;
KW   Nuclease; Nucleotidyltransferase; Phosphoprotein; Protease; Repeat;
KW   Ribosomal frameshifting; RNA-binding; RNA-directed DNA polymerase;
KW   Transferase; Viral genome integration; Viral nucleoprotein; Virion;
KW   Virus entry into host cell; Zinc; Zinc-finger.
FT   INIT_MET        1
FT                   /note="Removed; by host"
FT                   /evidence="ECO:0000255"
FT   CHAIN           2..1462
FT                   /note="Gag-Pro-Pol polyprotein"
FT                   /id="PRO_0000259828"
FT   CHAIN           2..130
FT                   /note="Matrix protein p19"
FT                   /id="PRO_0000259829"
FT   CHAIN           131..344
FT                   /note="Capsid protein p24"
FT                   /id="PRO_0000259830"
FT   CHAIN           345..449
FT                   /note="Nucleocapsid protein p15-pro"
FT                   /id="PRO_0000259831"
FT   CHAIN           450..574
FT                   /note="Protease"
FT                   /id="PRO_0000259832"
FT   PEPTIDE         575..582
FT                   /note="p1"
FT                   /id="PRO_0000259833"
FT   CHAIN           583..1167
FT                   /note="Reverse transcriptase/ribonuclease H, p62 subunit"
FT                   /id="PRO_0000038873"
FT   CHAIN           583..1021
FT                   /note="Reverse transcriptase/ribonuclease H, p49 subunit"
FT                   /id="PRO_0000442547"
FT   CHAIN           1168..1462
FT                   /note="Integrase"
FT                   /id="PRO_0000038874"
FT   DOMAIN          476..554
FT                   /note="Peptidase A2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00275"
FT   DOMAIN          614..804
FT                   /note="Reverse transcriptase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT   DOMAIN          1031..1165
FT                   /note="RNase H type-1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT   DOMAIN          1219..1388
FT                   /note="Integrase catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00457"
FT   ZN_FING         355..372
FT                   /note="CCHC-type 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT   ZN_FING         378..395
FT                   /note="CCHC-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT   DNA_BIND        1393..1443
FT                   /note="Integrase-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00506"
FT   REGION          93..144
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           118..121
FT                   /note="PPXY motif"
FT                   /evidence="ECO:0000250|UniProtKB:P03345"
FT   MOTIF           124..127
FT                   /note="PTAP/PSAP motif"
FT                   /evidence="ECO:0000250|UniProtKB:P03345"
FT   ACT_SITE        481
FT                   /note="For protease activity; shared with dimeric partner"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT   BINDING         680
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:0000255|PROSITE-ProRule:PRU00405"
FT   BINDING         755
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:0000255|PROSITE-ProRule:PRU00405"
FT   BINDING         756
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:0000255|PROSITE-ProRule:PRU00405"
FT   BINDING         1040
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:0000255|PROSITE-ProRule:PRU00408"
FT   BINDING         1074
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:0000255|PROSITE-ProRule:PRU00408"
FT   BINDING         1096
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:0000255|PROSITE-ProRule:PRU00408"
FT   BINDING         1157
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:0000255|PROSITE-ProRule:PRU00408"
FT   BINDING         1230
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="3"
FT                   /ligand_note="catalytic; for integrase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00457"
FT   BINDING         1287
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="3"
FT                   /ligand_note="catalytic; for integrase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00457"
FT   SITE            130..131
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000269|PubMed:10037763"
FT   SITE            344..345
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000269|PubMed:10037763"
FT   SITE            449..450
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000269|PubMed:10037763"
FT   SITE            574..575
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000269|PubMed:10037763,
FT                   ECO:0000269|PubMed:16682197"
FT   SITE            582..583
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000303|PubMed:15102858"
FT   SITE            1021..1022
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000269|PubMed:16368688"
FT   SITE            1167..1168
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000269|PubMed:12504078"
FT   MOD_RES         105
FT                   /note="Phosphoserine; by host MAPK1"
FT                   /evidence="ECO:0000250|UniProtKB:P03345"
FT   LIPID           2
FT                   /note="N-myristoyl glycine; by host"
FT                   /evidence="ECO:0000255, ECO:0000269|PubMed:11333909"
FT   VARIANT         440..441
FT                   /note="LP -> FL"
FT   VARIANT         569
FT                   /note="R -> G"
FT   VARIANT         621
FT                   /note="P -> S"
FT   MUTAGEN         2
FT                   /note="G->A: Complete loss of myristoylation the
FT                   polyprotein. The concomitent loss of binding to the host
FT                   cell membrane impairs the formation of viral particles."
FT                   /evidence="ECO:0000269|PubMed:11333909"
FT   MUTAGEN         486
FT                   /note="M->A,D,N: Complete loss of protease activity."
FT                   /evidence="ECO:0000269|PubMed:15102858"
FT   MUTAGEN         486
FT                   /note="M->I: Almost no effect on protease activity."
FT                   /evidence="ECO:0000269|PubMed:15102858"
FT   MUTAGEN         486
FT                   /note="M->V: Decrease in protease activity."
FT                   /evidence="ECO:0000269|PubMed:15102858"
FT   MUTAGEN         506
FT                   /note="L->G: Complete loss of protease activity."
FT                   /evidence="ECO:0000269|PubMed:15102858"
FT   MUTAGEN         508
FT                   /note="A->I: Decrease in protease activity."
FT                   /evidence="ECO:0000269|PubMed:15102858"
FT   MUTAGEN         516
FT                   /note="F->Q: Complete loss of protease activity."
FT                   /evidence="ECO:0000269|PubMed:15102858"
FT   MUTAGEN         545
FT                   /note="N->T: Almost complete loss of protease activity."
FT                   /evidence="ECO:0000269|PubMed:15102858"
FT   MUTAGEN         546
FT                   /note="N->P: Almost complete loss of protease activity."
FT                   /evidence="ECO:0000269|PubMed:15102858"
FT   MUTAGEN         547
FT                   /note="W->V: Almost complete loss of protease activity."
FT                   /evidence="ECO:0000269|PubMed:15102858"
FT   CONFLICT        545..547
FT                   /note="NNW -> GSM (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        569
FT                   /note="R -> G (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        592
FT                   /note="Q -> E (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   STRAND          451..453
FT                   /evidence="ECO:0007829|PDB:2B7F"
FT   STRAND          456..458
FT                   /evidence="ECO:0007829|PDB:4YDG"
FT   STRAND          461..467
FT                   /evidence="ECO:0007829|PDB:2B7F"
FT   STRAND          469..471
FT                   /evidence="ECO:0007829|PDB:2B7F"
FT   STRAND          474..480
FT                   /evidence="ECO:0007829|PDB:2B7F"
FT   STRAND          484..486
FT                   /evidence="ECO:0007829|PDB:2B7F"
FT   STRAND          488..490
FT                   /evidence="ECO:0007829|PDB:2B7F"
FT   HELIX           491..493
FT                   /evidence="ECO:0007829|PDB:2B7F"
FT   STRAND          500..502
FT                   /evidence="ECO:0007829|PDB:2B7F"
FT   STRAND          505..507
FT                   /evidence="ECO:0007829|PDB:2B7F"
FT   STRAND          510..521
FT                   /evidence="ECO:0007829|PDB:2B7F"
FT   STRAND          523..526
FT                   /evidence="ECO:0007829|PDB:2B7F"
FT   STRAND          534..537
FT                   /evidence="ECO:0007829|PDB:2B7F"
FT   STRAND          540..542
FT                   /evidence="ECO:0007829|PDB:2B7F"
FT   HELIX           552..557
FT                   /evidence="ECO:0007829|PDB:2B7F"
FT   STRAND          561..563
FT                   /evidence="ECO:0007829|PDB:2B7F"
SQ   SEQUENCE   1462 AA;  162512 MW;  DCC70251EC729E87 CRC64;
     MGQIFSRSAS PIPRPPRGLA AHHWLNFLQA AYRLEPGPSS YDFHQLKKFL KIALETPARI
     CPINYSLLAS LLPKGYPGRV NEILHILIQT QAQIPSRPAP PPPSSPTHDP PDSDPQIPPP
     YVEPTAPQVL PVMHPHGAPP NHRPWQMKDL QAIKQEVSQA APGSPQFMQT IRLAVQQFDP
     TAKDLQDLLQ YLCSSLVASL HHQQLDSLIS EAETRGITGY NPLAGPLRVQ ANNPQQQGLR
     REYQQLWLAA FAALPGSAKD PSWASILQGL EEPYHAFVER LNIALDNGLP EGTPKDPILR
     SLAYSNANKE CQKLLQARGH TNSPLGDMLR ACQTWTPKDK TKVLVVQPKK PPPNQPCFRC
     GKAGHWSRDC TQPRPPPGPC PLCQDPTHWK RDCPRLKPTI PEPEPEEDAL LLDLPADIPH
     PKNLHRGGGL TSPPTLQQVL PNQDPASILP VIPLDPARRP VIKAQVDTQT SHPKTIEALL
     DTGADMTVLP IALFSSNTPL KNTSVLGAGG QTQDHFKLTS LPVLIRLPFR TTPIVLTSCL
     VDTKNNWAII GRDALQQCQG VLYLPEAKRP PVILPIQAPA VLGLEHLPRP PQISQFPLNP
     ERLQALQHLV RKALEAGHIE PYTGPGNNPV FPVKKANGTW RFIHDLRATN SLTIDLSSSS
     PGPPDLSSLP TTLAHLQTID LRDAFFQIPL PKQFQPYFAF TVPQQCNYGP GTRYAWKVLP
     QGFKNSPTLF EMQLAHILQP IRQAFPQCTI LQYMDDILLA SPSHEDLLLL SEATMASLIS
     HGLPVSENKT QQTPGTIKFL GQIISPNHLT YDAVPTVPIR SRWALPELQA LLGEIQWVSK
     GTPTLRQPLH SLYCALQRHT DPRDQIYLNP SQVQSLVQLR QALSQNCRSR LVQTLPLLGA
     IMLTLTGTTT VVFQSKEQWP LVWLHAPLPH TSQCPWGQLL ASAVLLLDKY TLQSYGLLCQ
     TIHHNISTQT FNQFIQTSDH PSVPILLHHS HRFKNLGAQT GELWNTFLKT AAPLAPVKAL
     MPVFTLSPVI INTAPCLFSD GSTSRAAYIL WDKQILSQRS FPLPPPHKSA QRAELLGLLH
     GLSSARSWRC LNIFLDSKYL YHYLRTLALG TFQGRSSQAP FQALLPRLLS RKVVYLHHVR
     SHTNLPDPIS RLNALTDALL ITPVLQLSPA ELHSFTHCGQ TALTLQGATT TEASNILRSC
     HACRGGNPQH QMPRGHIRRG LLPNHIWQGD ITHFKYKNTL YRLHVWVDTF SGAISATQKR
     KETSSEAISS LLQAIAHLGK PSYINTDNGP AYISQDFLNM CTSLAIRHTT HVPYNPTSSG
     LVERSNGILK TLLYKYFTDK PDLPMDNALS IALWTINHLN VLTNCHKTRW QLHHSPRLQP
     IPETRSLSNK QTHWYYFKLP GLNSRQWKGP QEALQEAAGA ALIPVSASSA QWIPWRLLKR
     AACPRPVGGP ADPKEKDLQH HG
//