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Protein

Pro-Pol polyprotein

Gene

pol

Organism
Feline foamy virus (FFV) (Feline syncytial virus)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Protein inferred from homologyi

Functioni

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-Lys1,2 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).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 at least the viral genome, matrix protein, and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from the 3' end of the viral DNA right (U5) end, leaving the left (U3) intact. In the second step, the PIC enters cell nucleus. This process is mediated through the integrase and allows the virus to infect both dividing (nuclear membrane disassembled) and G1/S-arrested cells (active translocation), but with no viral gene expression in the latter. In 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. It is however not clear how integration then proceeds to resolve the asymmetrical cleavage of viral DNA (By similarity).By similarity

Catalytic activityi

Endonucleolytic cleavage to 5'-phosphomonoester.PROSITE-ProRule annotation
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).PROSITE-ProRule annotation

Cofactori

Protein has several cofactor binding sites:
  • Mg2+By similarityNote: Binds 2 magnesium ions for reverse transcriptase polymerase activity.By similarity
  • Mg2+By similarityNote: Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding.By similarity
  • Mg2+By similarityNote: Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei21 – 211For protease activityPROSITE-ProRule annotation
Metal bindingi249 – 2491Magnesium; catalytic; for reverse transcriptase activityBy similarity
Metal bindingi311 – 3111Magnesium; catalytic; for reverse transcriptase activityBy similarity
Metal bindingi312 – 3121Magnesium; catalytic; for reverse transcriptase activityBy similarity
Metal bindingi595 – 5951Magnesium; catalytic; for RNase H activityBy similarity
Metal bindingi643 – 6431Magnesium; catalytic; for RNase H activityBy similarity
Metal bindingi666 – 6661Magnesium; catalytic; for RNase H activityBy similarity
Metal bindingi737 – 7371Magnesium; catalytic; for RNase H activityBy similarity
Metal bindingi875 – 8751Magnesium; catalytic; for integrase activityBy similarity
Metal bindingi937 – 9371Magnesium; catalytic; for integrase activityBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Aspartyl protease, DNA-directed DNA polymerase, Endonuclease, Hydrolase, Nuclease, Nucleotidyltransferase, Protease, RNA-directed DNA polymerase, Transferase

Keywords - Biological processi

DNA integration, DNA recombination, Viral genome integration, Viral penetration into host nucleus, Virus entry into host cell

Keywords - Ligandi

Magnesium, Metal-binding, RNA-binding

Protein family/group databases

MEROPSiA09.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Pro-Pol polyprotein
Alternative name(s):
Pr125Pol
Cleaved into the following 4 chains:
Alternative name(s):
p87Pro-RT-RNaseH
Alternative name(s):
p65Pro-RT
Ribonuclease H (EC:3.1.26.4)
Short name:
RNase H
Integrase (EC:2.7.7.-By similarity, EC:3.1.-.-By similarity)
Short name:
IN
Alternative name(s):
p42In
Gene namesi
Name:pol
OrganismiFeline foamy virus (FFV) (Feline syncytial virus)
Taxonomic identifieri53182 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeSpumaretrovirinaeSpumavirus
Virus hostiFelis catus (Cat) (Felis silvestris catus) [TaxID: 9685]
Proteomesi
  • UP000008763 Componenti: Genome

Subcellular locationi

Integrase :
Protease/Reverse transcriptase/ribonuclease H :

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11561156Pro-Pol polyproteinPRO_0000244980Add
BLAST
Chaini1 – 748748Protease/Reverse transcriptase/ribonuclease HBy similarityPRO_0000244981Add
BLAST
Chaini1 – 592592Protease/Reverse transcriptaseBy similarityPRO_0000244982Add
BLAST
Chaini593 – 748156Ribonuclease HBy similarityPRO_0000244983Add
BLAST
Chaini749 – 1143395IntegraseBy similarityPRO_0000244984Add
BLAST

Post-translational modificationi

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei592 – 5932Cleavage; by viral protease; partialBy similarity
Sitei748 – 7492Cleavage; by viral proteaseBy similarity

Proteomic databases

PRIDEiO93209.

Structurei

3D structure databases

ProteinModelPortaliO93209.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 140140Peptidase A9PROSITE-ProRule annotationAdd
BLAST
Domaini183 – 360178Reverse transcriptasePROSITE-ProRule annotationAdd
BLAST
Domaini586 – 745160RNase HPROSITE-ProRule annotationAdd
BLAST
Domaini869 – 1025157Integrase catalyticPROSITE-ProRule annotationAdd
BLAST

Domaini

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).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,D(35)E motif is independently essential for the 3'-processing and strand transfer activities of purified integrase protein (By similarity).By similarity

Sequence similaritiesi

Contains 1 integrase catalytic domain.PROSITE-ProRule annotation
Contains 1 peptidase A9 domain.PROSITE-ProRule annotation
Contains 1 reverse transcriptase domain.PROSITE-ProRule annotation
Contains 1 RNase H domain.PROSITE-ProRule annotation

Family and domain databases

Gene3Di3.30.420.10. 2 hits.
InterProiIPR001584. Integrase_cat-core.
IPR012337. RNaseH-like_dom.
IPR002156. RNaseH_domain.
IPR000477. RT_dom.
IPR001641. Spumavirus_A9.
[Graphical view]
PfamiPF00075. RNase_H. 1 hit.
PF00665. rve. 1 hit.
PF00078. RVT_1. 1 hit.
PF03539. Spuma_A9PTase. 1 hit.
[Graphical view]
PRINTSiPR00920. SPUMVIRPTASE.
ProDomiPD013079. Peptidase_A9_cat. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF53098. SSF53098. 2 hits.
PROSITEiPS51531. FV_PR. 1 hit.
PS50994. INTEGRASE. 1 hit.
PS50879. RNASE_H. 1 hit.
PS50878. RT_POL. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O93209-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDLLKPLTVE RKGVKIKGYW DSQADITCVP KDLLQGEEPV RQQNVTTIHG
60 70 80 90 100
TQEGDVYYVN LKIDGRRINT EVIGTTLDYA IITPGDVPWI LKKPLELTIK
110 120 130 140 150
LDLEEQQGTL LNNSILSKKG KEELKQLFEK YSALWQSWEN QVGHRRIRPH
160 170 180 190 200
KIATGTVKPT PQKQYHINPK AKPDIQIVIN DLLKQGVLIQ KESTMNTPVY
210 220 230 240 250
PVPKPNGRWR MVLDYRAVNK VTPLIAVQNQ HSYGILGSLF KGRYKTTIDL
260 270 280 290 300
SNGFWAHPIV PEDYWITAFT WQGKQYCWTV LPQGFLNSPG LFTGDVVDLL
310 320 330 340 350
QGIPNVEVYV DDVYISHDSE KEHLEYLDIL FNRLKEAGYI ISLKKSNIAN
360 370 380 390 400
SIVDFLGFQI TNEGRGLTDT FKEKLENITA PTTLKQLQSI LGLLNFARNF
410 420 430 440 450
IPDFTELIAP LYALIPKSTK NYVPWQIEHS TTLETLITKL NGAEYLQGRK
460 470 480 490 500
GDKTLIMKVN ASYTTGYIRY YNEGEKKPIS YVSIVFSKTE LKFTELEKLL
510 520 530 540 550
TTVHKGLLKA LDLSMGQNIH VYSPIVSMQN IQKTPQTAKK ALASRWLSWL
560 570 580 590 600
SYLEDPRIRF FYDPQMPALK DLPAVDTGKD NKKHPSNFQH IFYTDGSAIT
610 620 630 640 650
SPTKEGHLNA GMGIVYFINK DGNLQKQQEW SISLGNHTAQ FAEIAAFEFA
660 670 680 690 700
LKKCLPLGGN ILVVTDSNYV AKAYNEELDV WASNGFVNNR KKPLKHISKW
710 720 730 740 750
KSVADLKRLR PDVVVTHEPG HQKLDSSPHA YGNNLADQLA TQASFKVHMT
760 770 780 790 800
KNPKLDIEQI KAIQACQNNE RLPVGYPKQY TYELQNNKCM VLRKDGWREI
810 820 830 840 850
PPSRERYKLI KEAHNISHAG REAVLLKIQE NYWWPKMKKD ISSFLSTCNV
860 870 880 890 900
CKMVNPLNLK PISPQAIVHP TKPFDKFYMD YIGPLPPSEG YVHVLVVVDA
910 920 930 940 950
ATGFTWLYPT KAQTSKATIK VLNHLTGLAI PKVLHSDQGS AFTSEEFAQW
960 970 980 990 1000
AKERNIQLEF STPYHPQSSG KVERKNSEIK KLLTKLLVGR PLKWYNLISS
1010 1020 1030 1040 1050
VQLALNNTHV VSTKYTPHQL MFGIDCNLPF ANKDTLDWTR EEELALLQEI
1060 1070 1080 1090 1100
RESLQHPVQP PTCSGWSPYV GQLVQERVYR PSQLRPKWRK PTKVLEILNP
1110 1120 1130 1140 1150
RTVIIVDHLG QRKSVSIDNL KPTAHQHNGT RTCDDPEGMD GMECSQTTTE

TSVDSS
Length:1,156
Mass (Da):131,499
Last modified:November 1, 1998 - v1
Checksum:i74C8A66CCA10A712
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ223851 Genomic RNA. Translation: CAA11581.1.
Y08851 Genomic DNA. Translation: CAA70075.1.
RefSeqiNP_056914.1. NC_001871.1.

Genome annotation databases

GeneIDi2717067.
KEGGivg:2717067.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ223851 Genomic RNA. Translation: CAA11581.1.
Y08851 Genomic DNA. Translation: CAA70075.1.
RefSeqiNP_056914.1. NC_001871.1.

3D structure databases

ProteinModelPortaliO93209.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiA09.001.

Proteomic databases

PRIDEiO93209.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi2717067.
KEGGivg:2717067.

Family and domain databases

Gene3Di3.30.420.10. 2 hits.
InterProiIPR001584. Integrase_cat-core.
IPR012337. RNaseH-like_dom.
IPR002156. RNaseH_domain.
IPR000477. RT_dom.
IPR001641. Spumavirus_A9.
[Graphical view]
PfamiPF00075. RNase_H. 1 hit.
PF00665. rve. 1 hit.
PF00078. RVT_1. 1 hit.
PF03539. Spuma_A9PTase. 1 hit.
[Graphical view]
PRINTSiPR00920. SPUMVIRPTASE.
ProDomiPD013079. Peptidase_A9_cat. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF53098. SSF53098. 2 hits.
PROSITEiPS51531. FV_PR. 1 hit.
PS50994. INTEGRASE. 1 hit.
PS50879. RNASE_H. 1 hit.
PS50878. RT_POL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Characterization of the genome of feline foamy virus and its proteins shows distinct features different from those of primate Spumaviruses."
    Winkler I., Bodem J., Haas L., Zemba M., Delius H., Flower R., Fluegel R.M., Loechelt M.
    J. Virol. 71:6727-6741(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Detection of subgenomic cDNAs and mapping of feline foamy virus mRNAs reveals complex patterns of transcription."
    Bodem J., Loechelt M., Delius H., Fluegel R.M.
    Virology 244:417-426(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    Strain: Isolate FUV.

Entry informationi

Entry nameiPOL_FFV
AccessioniPrimary (citable) accession number: O93209
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: November 1, 1998
Last modified: June 8, 2016
This is version 95 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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.
Foamy viruses are distinct from other retroviruses in many respects. Their protease is active as an uncleaved Pro-Pol protein. Mature particles do not include the usual processed retroviral structural protein (MA, CA and NC), but instead contain two large Gag proteins. Their functional nucleic acid appears to be either RNA or dsDNA (up to 20% of extracellular particles), because they probably proceed either to an early (before integration) or late reverse transcription (after assembly). Foamy viruses have the ability to retrotranspose intracellularly with high efficiency. They bud predominantly into the endoplasmic reticulum (ER) and occasionally at the plasma membrane. Budding requires the presence of Env proteins. Most viral particles probably remain within the infected cell.

Keywords - Technical termi

Complete proteome, Multifunctional enzyme

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.