ID   POL_AVIRE               Reviewed;        1152 AA.
AC   P03360; Q2Q1R2;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   20-DEC-2017, sequence version 2.
DT   28-JAN-2026, entry version 115.
DE   RecName: Full=Gag-Pol polyprotein;
DE   Contains:
DE     RecName: Full=Protease;
DE              EC=3.4.23.-;
DE   Contains:
DE     RecName: Full=Reverse transcriptase/ribonuclease H;
DE              Short=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:0000269|PubMed:24124581};
DE              EC=3.1.-.- {ECO:0000269|PubMed:24124581};
DE   Flags: Fragment;
GN   Name=pol;
OS   Avian reticuloendotheliosis virus.
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Gammaretrovirus;
OC   Gammaretrovirus aviretend.
OX   NCBI_TaxID=11636;
OH   NCBI_TaxID=8976; Galliformes.
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=A;
RX   PubMed=16497405; DOI=10.1016/j.virusres.2006.01.011;
RA   Bohls R.L., Linares J.A., Gross S.L., Ferro P.J., Silvy N.J.,
RA   Collisson E.W.;
RT   "Phylogenetic analyses indicate little variation among
RT   reticuloendotheliosis viruses infecting avian species, including the
RT   endangered Attwater's prairie chicken.";
RL   Virus Res. 119:187-194(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 680-1152.
RC   STRAIN=A;
RX   PubMed=6090694; DOI=10.1128/jvi.52.1.172-182.1984;
RA   Wilhelmsen K.C., Eggleton K., Temin H.M.;
RT   "Nucleic acid sequences of the oncogene v-rel in reticuloendotheliosis
RT   virus strain T and its cellular homolog, the proto-oncogene c-rel.";
RL   J. Virol. 52:172-182(1984).
RN   [3]
RP   CATALYTIC ACTIVITY (INTEGRASE), CHARACTERIZATION (INTEGRASE), COFACTOR
RP   (INTEGRASE), AND FUNCTION (INTEGRASE).
RX   PubMed=24124581; DOI=10.1371/journal.pone.0076638;
RA   Ballandras-Colas A., Naraharisetty H., Li X., Serrao E., Engelman A.;
RT   "Biochemical characterization of novel retroviral integrase proteins.";
RL   PLoS ONE 8:E76638-E76638(2013).
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. {ECO:0000255|PROSITE-
CC       ProRule:PRU00275}.
CC   -!- FUNCTION: [Reverse transcriptase/ribonuclease H]: RT is a
CC       multifunctional enzyme that converts the viral dimeric RNA genome into
CC       dsDNA in the cytoplasm, shortly after virus entry into the cell. This
CC       enzyme displays a DNA polymerase activity that can copy either DNA or
CC       RNA templates, and a ribonuclease H (RNase H) activity that cleaves the
CC       RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5'
CC       endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires
CC       many steps. A tRNA binds to the primer-binding site (PBS) situated at
CC       the 5' end of the viral RNA. RT uses the 3' end of the tRNA primer to
CC       perfom a short round of RNA-dependent minus-strand DNA synthesis. The
CC       reading proceeds through the U5 region and ends after the repeated (R)
CC       region which is present at both ends of viral RNA. The portion of the
CC       RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA
CC       product attached to the tRNA primer. This ssDNA/tRNA hybridizes with
CC       the identical R region situated at the 3' end of viral RNA. This
CC       template exchange, known as minus-strand DNA strong stop transfer, can
CC       be either intra- or intermolecular. RT uses the 3' end of this newly
CC       synthesized short ssDNA to perfom 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       primers. PPT and tRNA primers are then removed by RNase H. The 3' and
CC       5' 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. {ECO:0000255|PROSITE-
CC       ProRule:PRU00405}.
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|PubMed:24124581}.
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   -!- CATALYTIC ACTIVITY:
CC       Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.4;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU00408};
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   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000269|PubMed:24124581};
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:24124581};
CC       Note=Magnesium or manganese ions are required for integrase activity.;
CC   -!- SUBUNIT: [Reverse transcriptase/ribonuclease H]: The reverse
CC       transcriptase is a monomer. {ECO:0000255|PROSITE-ProRule:PRU00405}.
CC   -!- PTM: [Gag-Pol polyprotein]: Specific enzymatic cleavages in vivo yield
CC       mature proteins. {ECO:0000305}.
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: Strain A is a helper virus of the strain T.
CC   -!- SIMILARITY: Belongs to the retroviral Pol polyprotein family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA25685.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; DQ237900; ABC26818.1; -; Genomic_DNA.
DR   EMBL; X01455; CAA25685.1; ALT_FRAME; Genomic_RNA.
DR   PIR; A03959; A03959.
DR   SMR; P03360; -.
DR   GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:InterPro.
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: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:InterPro.
DR   GO; GO:0046718; P:symbiont entry into host cell; IEA:UniProtKB-KW.
DR   GO; GO:0044826; P:viral genome integration into host DNA; IEA:UniProtKB-KW.
DR   CDD; cd09273; RNase_HI_RT_Bel; 1.
DR   CDD; cd03715; RT_ZFREV_like; 1.
DR   FunFam; 3.30.70.270:FF:000020; Transposon Tf2-6 polyprotein-like Protein; 1.
DR   Gene3D; 1.10.340.70; -; 1.
DR   Gene3D; 2.30.30.850; -; 1.
DR   Gene3D; 3.10.20.370; -; 1.
DR   Gene3D; 3.30.70.270; -; 2.
DR   Gene3D; 2.40.70.10; Acid Proteases; 1.
DR   Gene3D; 3.10.10.10; HIV Type 1 Reverse Transcriptase, subunit A, domain 1; 1.
DR   Gene3D; 3.30.420.10; Ribonuclease H-like superfamily/Ribonuclease H; 2.
DR   InterPro; IPR043502; DNA/RNA_pol_sf.
DR   InterPro; IPR001584; Integrase_cat-core.
DR   InterPro; IPR040643; MLVIN_C.
DR   InterPro; IPR001995; Peptidase_A2_cat.
DR   InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR   InterPro; IPR018061; Retropepsins.
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; IPR051320; Viral_Replic_Matur_Polypro.
DR   InterPro; IPR015416; Znf_H2C2_histone_UAS-bd.
DR   PANTHER; PTHR33064:SF38; LRRGT00076-LIKE; 1.
DR   PANTHER; PTHR33064; POL PROTEIN; 1.
DR   Pfam; PF18697; MLVIN_C; 1.
DR   Pfam; PF00075; RNase_H; 1.
DR   Pfam; PF17919; RT_RNaseH_2; 1.
DR   Pfam; PF00665; rve; 1.
DR   Pfam; PF00077; RVP; 1.
DR   Pfam; PF00078; RVT_1; 1.
DR   Pfam; PF09337; zf-H2C2; 1.
DR   SUPFAM; SSF50630; Acid proteases; 1.
DR   SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR   SUPFAM; SSF53098; Ribonuclease H-like; 2.
DR   PROSITE; PS50175; ASP_PROT_RETROV; 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   DNA integration; DNA recombination; DNA-binding;
KW   DNA-directed DNA polymerase; Endonuclease; Hydrolase; Magnesium;
KW   Metal-binding; Multifunctional enzyme; Nuclease; Nucleotidyltransferase;
KW   RNA-binding; RNA-directed DNA polymerase; Transferase;
KW   Viral genome integration; Virus entry into host cell.
FT   CHAIN           <1..1152
FT                   /note="Gag-Pol polyprotein"
FT                   /id="PRO_0000125480"
FT   CHAIN           <1..78
FT                   /note="Protease"
FT                   /id="PRO_0000442467"
FT   CHAIN           79..751
FT                   /note="Reverse transcriptase/ribonuclease H"
FT                   /id="PRO_0000442468"
FT   CHAIN           752..1152
FT                   /note="Integrase"
FT                   /id="PRO_0000442469"
FT   DOMAIN          <1..52
FT                   /note="Peptidase A2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00275"
FT   DOMAIN          158..351
FT                   /note="Reverse transcriptase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT   DOMAIN          595..741
FT                   /note="RNase H type-1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT   DOMAIN          863..1020
FT                   /note="Integrase catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00457"
FT   REGION          1128..1152
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         228
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT   BINDING         302
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT   BINDING         303
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT   BINDING         604
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT   BINDING         642
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT   BINDING         663
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT   BINDING         733
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT   BINDING         874
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="3"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00457"
FT   BINDING         933
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="3"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00457"
FT   SITE            78..79
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000250|UniProtKB:P03355"
FT   SITE            751..752
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000250|UniProtKB:P03355"
FT   VARIANT         688
FT                   /note="G -> E"
FT                   /evidence="ECO:0000305"
FT   VARIANT         766
FT                   /note="N -> H"
FT                   /evidence="ECO:0000305"
FT   VARIANT         781
FT                   /note="P -> S"
FT                   /evidence="ECO:0000305"
FT   VARIANT         826
FT                   /note="L -> P"
FT                   /evidence="ECO:0000305"
FT   VARIANT         850
FT                   /note="G -> R"
FT                   /evidence="ECO:0000305"
FT   VARIANT         918
FT                   /note="H -> L"
FT                   /evidence="ECO:0000305"
FT   VARIANT         1111
FT                   /note="V -> A"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        680..682
FT                   /note="ERG -> KGE (in Ref. 2; CAA25685)"
FT                   /evidence="ECO:0000305"
FT   NON_TER         1
SQ   SEQUENCE   1152 AA;  128060 MW;  1268B817BF6FE2A6 CRC64;
     MSKESVAIIG ATGNIRNYPK SEGRLVDLGR GLVTHSFLVI PECPDPLLGR DLLQKLRATI
     SFTGEGPPEI RTEGKLLVTA PLEEEYRLFL EAPIQNVTLL EQWKREIPKV WAEINPPGLA
     STQAPIHVQL LSTALPVRVR QYPITLEAKR SLRETIRKFR AAGILRPVHS PWNTPLLPVR
     KSGTSEYRMV QDLREVNKRV ETIHPTVPNP YTLLSLLPPD RIWYSVLDLK DAFFCIPLAP
     ESQLIFAFEW ADAEEGESGQ LTWTRLPQGF KNSPTLFDEA LNRDLQGFRL DHPSVSLLQY
     VDDLLIAADT QAACLSATRD LLMTLAELGY RVSGKKAQLC QEEVTYLGFK IHKGSRSLSN
     SRTQAILQIP VPKTKRQVRE FLGTIGYCRL WIPGFAELAQ PLYAATRGGN DPLVWGEKEE
     EAFQSLKLAL TQPPALALPS LDKPFQLFVE ETSGAAKGVL TQALGPWKRP VAYLSKRLDP
     VAAGWPRCLR AIAAAALLTR EASKLTFGQD IEITSSHNLE SLLRSPPDKW LTNARITQYQ
     VLLLDPPRVR FKQTAALNPA TLLPETDDTL PIHHCLDTLD SLTSTRPDLT DQPLAQAEAT
     LFTDGSSYIR DGKRYAGAAV VTLDSVIWAE PLPIGTSAQK AELIALTKAL EWSKDKSVNI
     YTDSRYAFAT LHVHGMIYRE RGLLTAGGKA IKNAPEILAL LTAVWLPKRV AVMHCKGHQK
     DDAPTSTGNR RADEVAREVA IRPLSTQATI SDAPDMPDTE TPQYSNVEEA LGHRLRGTKD
     PAGWWHLPDG RLLLPRAVGR KVLEQTHRAT HLGESKLTEL VRKHYLICGI YRAARDITTR
     CVACAQVNPG AAPVEKGLNS RIRGAAPGEH WEVDFTEMIT AKGGYKYLLV LVDTFSGWVE
     AYPAKRETSQ VVIKHLIHDI IPRFGLPVQI GSDNGPAFVA KVTQQLCEAL NVSWKLHCAY
     RPQSSGQVER MNRTLKETIA KLRIETGGDW VSLLPQALLR ARCTPGREGL SPFEILYGLK
     PPVVPRVGCD KLASITNQTL LKSLQALQAT RSLARATLRD QLPQKEAQQD RTPLFQPGDL
     VFVKKHDFQQ LGPRWDGPYT VVLSTPTAVK VAGKTPWIHY SRLKKAPDNQ EEWTVSPTSD
     PLRVKLTRRA KP
//