POL_AVIRE
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 03-AUG-2022, entry version 104.
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.
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=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 -!- 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;
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 -!- 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 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: 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:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0044826; P:viral genome integration into host DNA; 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; IPR040643; MLVIN_C.
DR InterPro; IPR001995; Peptidase_A2_cat.
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; IPR015416; Znf_H2C2_histone_UAS-bd.
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; PF00078; RVT_1; 1.
DR Pfam; PF09337; zf-H2C2; 1.
DR SUPFAM; SSF50630; SSF50630; 1.
DR SUPFAM; SSF53098; SSF53098; 2.
DR SUPFAM; SSF56672; SSF56672; 1.
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
