POL_HTL1A
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 03-AUG-2022, entry version 162.
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.
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=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;
CC Evidence={ECO:0000255|PROSITE-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 swiching 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 PDBsum; 2B7F; -.
DR PDBsum; 4YDG; -.
DR BMRB; P03362; -.
DR SMR; P03362; -.
DR DrugCentral; P03362; -.
DR iPTMnet; P03362; -.
DR PRIDE; P03362; -.
DR BRENDA; 3.4.23.B8; 2706.
DR EvolutionaryTrace; P03362; -.
DR Proteomes; UP000007683; Genome.
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: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 Gene3D; 1.10.1200.30; -; 1.
DR Gene3D; 1.10.375.10; -; 1.
DR Gene3D; 2.40.70.10; -; 1.
DR Gene3D; 3.30.420.10; -; 2.
DR Gene3D; 3.30.70.270; -; 2.
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; IPR000721; Gag_p24_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; 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 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; SSF47836; SSF47836; 1.
DR SUPFAM; SSF47943; SSF47943; 1.
DR SUPFAM; SSF50122; SSF50122; 1.
DR SUPFAM; SSF50630; SSF50630; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
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; 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;
KW Reference proteome; Repeat; Ribosomal frameshifting; RNA-binding;
KW RNA-directed DNA polymerase; Transferase; Viral genome integration;
KW Viral nucleoprotein; Virion; 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 COMPBIAS 95..126
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 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
