Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9TTC1 (POL_KORV) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 76. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pro-Pol polyprotein
Alternative name(s):
Pr125Pol

Cleaved into the following 2 chains:

  1. Protease/Reverse transcriptase/ribonuclease H
    EC=2.7.7.49
    EC=2.7.7.7
    EC=3.1.26.4
    EC=3.4.23.-
    Alternative name(s):
    p87Pro-RT-RNaseH
  2. Integrase
    Short name=IN
    Alternative name(s):
    p42In
Gene names
Name:pro-pol
OrganismKoala retrovirus (KoRV) [Complete proteome]
Taxonomic identifier394239 [NCBI]
Taxonomic lineageVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeGammaretrovirusunclassified Gammaretrovirus
Virus hostPhascolarctos cinereus (Koala) [TaxID: 38626]

Protein attributes

Sequence length1127 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceInferred from homology

General annotation (Comments)

Function

The aspartyl protease activity mediates proteolytic cleavages of Gag and Pol polyproteins. The reverse transcriptase (RT) activity converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell (early reverse transcription) or after proviral DNA transcription (late reverse transcription). RT consists of a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for a polypurine tract (PPT) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPT that has not been removed by RNase H as primer. PPT and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends By similarity.

Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA. In the second step, the PIC access cell chromosomes during cell division. The third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5'-ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands (see above) are filled in and then ligated By similarity.

Catalytic activity

Endonucleolytic cleavage to 5'-phosphomonoester.

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).

Cofactor

Binds 2 magnesium ions for reverse transcriptase polymerase activity By similarity.

Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding By similarity.

Magnesium ions for integrase activity. Binds at least 1, maybe 2 magnesium ions By similarity.

Subcellular location

Integrase: Virion Potential. Host nucleus By similarity. Host cytoplasm Potential. Note: Nuclear at initial phase, cytoplasmic at assembly Potential.

Protease/Reverse transcriptase/ribonuclease H: Host nucleus By similarity. Host cytoplasm Potential. Note: Nuclear at initial phase, cytoplasmic at assembly Potential.

Domain

The reverse transcriptase/ribonuclease H (RT) is structured in five subdomains: finger, palm, thumb, connection and RNase H. Within the palm subdomain, the "primer grip" region is thought to be involved in the positioning of the primer terminus for accommodating the incoming nucleotide. The RNase H domain stabilizes the association of RT with primer-template By similarity.

Integrase core domain contains the D-x(n)-D-x(35)-E motif, named for the phylogenetically conserved glutamic acid and aspartic acid residues and the invariant 35 amino acid spacing between the second and third acidic residues. Each acidic residue of the D,D35E motif is independently essential for the 3'-processing and strand transfer activities of purified integrase protein By similarity.

Post-translational modification

Specific enzymatic cleavages in vivo by viral protease yield mature proteins. The protease is not cleaved off from Pol. Since cleavage efficiency is not optimal for all sites, long and active p65Pro-RT, p87Pro-RT-RNaseH and even some Pr125Pol are detected in infected cells By similarity.

Miscellaneous

The reverse transcriptase is an error-prone enzyme that lacks a proof-reading function. High mutations rate is a direct consequence of this characteristic. RT also displays frequent template switching leading to high recombination rate. Recombination mostly occurs between homologous regions of the two copackaged RNA genomes. If these two RNA molecules derive from different viral strains, reverse transcription will give rise to highly recombinated proviral DNAs.

Koala retrovirus is both a circulating virus and an endogenous retrovirus of koala, except in some isolated populations in south Australia.

Sequence similarities

Contains 1 integrase catalytic domain.

Contains 1 peptidase A2 domain.

Contains 1 reverse transcriptase domain.

Contains 1 RNase H domain.

Ontologies

Keywords
   Biological processDNA integration
DNA recombination
Viral genome integration
Virus entry into host cell
   Cellular componentHost cytoplasm
Host nucleus
Virion
   Coding sequence diversityRNA suppression of termination
   LigandMagnesium
Metal-binding
RNA-binding
   Molecular functionAspartyl protease
DNA-directed DNA polymerase
Endonuclease
Hydrolase
Nuclease
Nucleotidyltransferase
Protease
RNA-directed DNA polymerase
Transferase
   Technical termComplete proteome
Multifunctional enzyme
Gene Ontology (GO)
   Biological_processDNA integration

Inferred from electronic annotation. Source: UniProtKB-KW

DNA recombination

Inferred from electronic annotation. Source: UniProtKB-KW

establishment of integrated proviral latency

Inferred from electronic annotation. Source: UniProtKB-KW

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

viral entry into host cell

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componenthost cell cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

virion

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionDNA-directed DNA polymerase activity

Inferred from electronic annotation. Source: UniProtKB-KW

RNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA-DNA hybrid ribonuclease activity

Inferred from electronic annotation. Source: UniProtKB-EC

RNA-directed DNA polymerase activity

Inferred from electronic annotation. Source: UniProtKB-KW

aspartic-type endopeptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11271127Pro-Pol polyprotein
PRO_0000249431
Chain1 – ?742742Protease/Reverse transcriptase/ribonuclease H By similarity
PRO_0000249432
Chain?743 – 1127385Integrase By similarity
PRO_0000249433

Regions

Domain22 – 9271Peptidase A2
Domain202 – 393192Reverse transcriptase
Domain635 – 781147RNase H
Domain905 – 1063159Integrase catalytic

Sites

Metal binding2291Magnesium; catalytic; for reverse transcriptase activity By similarity
Metal binding3031Magnesium; catalytic; for reverse transcriptase activity By similarity
Metal binding3041Magnesium; catalytic; for reverse transcriptase activity By similarity
Metal binding6611Magnesium; catalytic; for RNase H activity By similarity
Metal binding7311Magnesium; catalytic; for RNase H activity By similarity
Metal binding9041Magnesium; catalytic; for integrase activity By similarity
Site?742 – ?7432Cleavage; by viral protease By similarity

Sequences

Sequence LengthMass (Da)Tools
Q9TTC1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 010ADD971CA957BF

FASTA1,127125,817
        10         20         30         40         50         60 
MGKMGSKRTV VAGATGSKVY PWTTKRLLKI GQKQVTHSFL VIPECPAPLL GRDLLTKLKA 

        70         80         90        100        110        120 
QIQFSTEGPQ VTWEDRPAMC LVLNLEEEYR LHEKPVPPSI DPSWLQLFPM VWAEKAGMGL 

       130        140        150        160        170        180 
ANQVPPVVVE LKSDASPVAV RQYPMSKEAR EGIRPHIQRF LDLGILVPCQ SPWNTPLLPV 

       190        200        210        220        230        240 
KKPGTNDYRP VQDLREVNKR VQDIHPTVPN PYNLLSSLPP SHTWYSVLDL KDAFFCLKLH 

       250        260        270        280        290        300 
PNSQPLFAFE WRDPEKGNTG QLTWTRLPQG FKNSPTLFDE ALHRDLASFR ALNPQVVMLQ 

       310        320        330        340        350        360 
YVDDLLVAAP TYRDCKEGTR RLLQELSKLG YRVSAKKAQL CREEVTYLGY LLKGGKRWLT 

       370        380        390        400        410        420 
PARKATVMKI PTPTTPRQVR EFLGTAGFCR LWIPGFASLA APLYPLTREK VPFTWTEAHQ 

       430        440        450        460        470        480 
EAFGRIKEAL LSAPALALPD LTKPFALYVD EKEGVARGVL TQTLGPWRRP VAYLSKKLDP 

       490        500        510        520        530        540 
VASGWPTCLK AIAAVALLLK DADKLTLGQN VLVIAPHNLE SIVRQPPDRW MTNARMTHYQ 

       550        560        570        580        590        600 
SLLLNERVSF APPAILNPAT LLPVESDDTP IHICSEILAE ETGTRPDLRD QPLPGVPAWY 

       610        620        630        640        650        660 
TDGSSFIMDG RRQAGAAIVD NKRTVWASNL PEGTSAQKAE LIALTQALRL AEGKSINIYT 

       670        680        690        700        710        720 
DSRYAFATAH VHGAIYKQRG LLTSAGKDIK NKEEILALLE AIHLPKRVAI IHCPGHQRGT 

       730        740        750        760        770        780 
DPVATGNRKA DEAAKQAAQS TRILTETTKN QEHFEPTRGK IKPRELTPDQ GREFIQRLHQ 

       790        800        810        820        830        840 
LTHLGPDKLL QLVGRTSFHI PNLQSVVREI TSKCQVCAVT NAVTTYREPG RRQRGDRPGV 

       850        860        870        880        890        900 
YWEVDFTEVK PGRYGNRYLL VFIDTFSGWV EAFPTKTETA LTVCKKILEE ILPRFGIPKV 

       910        920        930        940        950        960 
LGSDNGPAFV AQVSQGLATQ LGIDWKLHCA YRPQSSGQVE RMNRTIKETL TKLALETGGK 

       970        980        990       1000       1010       1020 
DWVTLLPLAL LRARNTPGQF GLTPYEILHG GPPPVLASGE VVGSNGDFFP VLFTHLKALE 

      1030       1040       1050       1060       1070       1080 
VVRTQIWDQI KEAYRPGTVA IPHPFQVGDR VLVRRHRSGS LEPRWKGPYL VLLTTPTAVK 

      1090       1100       1110       1120 
VDGIAAWVHA SHLKPAPPGA PDESWELEKT DHPLKLRVRR RRNESTA 

« Hide

References

[1]"The nucleotide sequence of koala (Phascolarctos cinereus) retrovirus: a novel type C endogenous virus related to Gibbon ape leukemia virus."
Hanger J.J., Bromham L.D., McKee J.J., O'Brien T.M., Robinson W.F.
J. Virol. 74:4264-4272(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF151794 Genomic DNA. Translation: AAF15098.1.

3D structure databases

ProteinModelPortalQ9TTC1.
SMRQ9TTC1. Positions 103-552, 583-738.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

MEROPSA02.020.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D3.30.420.10. 2 hits.
InterProIPR001584. Integrase_cat-core.
IPR018061. Pept_A2A_retrovirus_sg.
IPR001995. Peptidase_A2_cat.
IPR021109. Peptidase_aspartic_dom.
IPR012337. RNaseH-like_dom.
IPR002156. RNaseH_domain.
IPR000477. RT_dom.
[Graphical view]
PfamPF00075. RNase_H. 1 hit.
PF00665. rve. 1 hit.
PF00077. RVP. 1 hit.
PF00078. RVT_1. 1 hit.
[Graphical view]
SUPFAMSSF50630. SSF50630. 1 hit.
SSF53098. SSF53098. 2 hits.
PROSITEPS50175. ASP_PROT_RETROV. 1 hit.
PS50994. INTEGRASE. 1 hit.
PS50879. RNASE_H. 1 hit.
PS50878. RT_POL. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry namePOL_KORV
AccessionPrimary (citable) accession number: Q9TTC1
Entry history
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 76 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries