O93209 (POL_FFV) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pro-Pol polyprotein

Alternative name(s):
Pr125Pol

Cleaved into the following 4 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. Protease/Reverse transcriptase
   EC=2.7.7.49
   EC=2.7.7.7
   EC=3.4.23.-
   Alternative name(s):
   p65Pro-RT
3. Ribonuclease H
   Short name=RNase H
   EC=3.1.26.4
4. Integrase
   Short name=IN
   Alternative name(s):
   p42In

Gene names

Name:

pol

Organism

Feline foamy virus (FFV) (Feline syncytial virus) [Complete proteome]

Taxonomic identifier

53182 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Spumaretrovirinae › Spumavirus

Virus host

Felis catus (Cat) (Felis silvestris catus) [TaxID: 9685]

Protein attributes

Sequence length	1156 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Inferred 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-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. 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.
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 accomodating 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,D(35)E 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. 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.
Sequence similarities	Contains 1 integrase catalytic domain. Contains 1 peptidase A9 domain. Contains 1 reverse transcriptase domain. Contains 1 RNase H domain.

Ontologies

Keywords
Biological process	DNA integration DNA recombination Initiation of viral infection Viral genome integration Viral penetration into host nucleus
Cellular component	Host cytoplasm Host nucleus Virion
Ligand	Magnesium Metal-binding RNA-binding
Molecular function	Aspartyl protease DNA-directed DNA polymerase Endonuclease Hydrolase Nuclease Nucleotidyltransferase Protease RNA-directed DNA polymerase Transferase
Technical term	Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	DNA integration Inferred from electronic annotation. Source: UniProtKB-KW DNA recombination Inferred from electronic annotation. Source: UniProtKB-KW RNA-dependent DNA replication Inferred from electronic annotation. Source: InterPro proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	host 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 function	DNA-directed DNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: UniProtKB-KW 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 ribonuclease H activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1156	1156	Pro-Pol polyprotein		PRO_0000244980
	Chain	1 – 748	748	Protease/Reverse transcriptase/ribonuclease H By similarity		PRO_0000244981
	Chain	1 – 592	592	Protease/Reverse transcriptase By similarity		PRO_0000244982
	Chain	593 – 748	156	Ribonuclease H By similarity		PRO_0000244983
	Chain	749 – 1143	395	Integrase By similarity		PRO_0000244984
Regions
	Domain	1 – 140	140	Peptidase A9
	Domain	183 – 360	178	Reverse transcriptase
	Domain	586 – 745	160	RNase H
	Domain	869 – 1025	157	Integrase catalytic
Sites
	Active site	21	1	For protease activity By similarity
	Metal binding	249	1	Magnesium; catalytic; for reverse transcriptase activity By similarity
	Metal binding	311	1	Magnesium; catalytic; for reverse transcriptase activity By similarity
	Metal binding	312	1	Magnesium; catalytic; for reverse transcriptase activity By similarity
	Metal binding	595	1	Magnesium; catalytic; for RNase H activity By similarity
	Metal binding	643	1	Magnesium; catalytic; for RNase H activity By similarity
	Metal binding	666	1	Magnesium; catalytic; for RNase H activity By similarity
	Metal binding	737	1	Magnesium; catalytic; for RNase H activity By similarity
	Metal binding	875	1	Magnesium; catalytic; for integrase activity By similarity
	Metal binding	937	1	Magnesium; catalytic; for integrase activity By similarity
	Site	592 – 593	2	Cleavage; by viral protease; partial By similarity
	Site	748 – 749	2	Cleavage; by viral protease By similarity

Sequences

	Sequence		Length	Mass (Da)
	O93209 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 74C8A66CCA10A712	FASTA	1,156	131,499
	10 20 30 40 50 60 MDLLKPLTVE RKGVKIKGYW DSQADITCVP KDLLQGEEPV RQQNVTTIHG TQEGDVYYVN 70 80 90 100 110 120 LKIDGRRINT EVIGTTLDYA IITPGDVPWI LKKPLELTIK LDLEEQQGTL LNNSILSKKG 130 140 150 160 170 180 KEELKQLFEK YSALWQSWEN QVGHRRIRPH KIATGTVKPT PQKQYHINPK AKPDIQIVIN 190 200 210 220 230 240 DLLKQGVLIQ KESTMNTPVY PVPKPNGRWR MVLDYRAVNK VTPLIAVQNQ HSYGILGSLF 250 260 270 280 290 300 KGRYKTTIDL SNGFWAHPIV PEDYWITAFT WQGKQYCWTV LPQGFLNSPG LFTGDVVDLL 310 320 330 340 350 360 QGIPNVEVYV DDVYISHDSE KEHLEYLDIL FNRLKEAGYI ISLKKSNIAN SIVDFLGFQI 370 380 390 400 410 420 TNEGRGLTDT FKEKLENITA PTTLKQLQSI LGLLNFARNF IPDFTELIAP LYALIPKSTK 430 440 450 460 470 480 NYVPWQIEHS TTLETLITKL NGAEYLQGRK GDKTLIMKVN ASYTTGYIRY YNEGEKKPIS 490 500 510 520 530 540 YVSIVFSKTE LKFTELEKLL TTVHKGLLKA LDLSMGQNIH VYSPIVSMQN IQKTPQTAKK 550 560 570 580 590 600 ALASRWLSWL SYLEDPRIRF FYDPQMPALK DLPAVDTGKD NKKHPSNFQH IFYTDGSAIT 610 620 630 640 650 660 SPTKEGHLNA GMGIVYFINK DGNLQKQQEW SISLGNHTAQ FAEIAAFEFA LKKCLPLGGN 670 680 690 700 710 720 ILVVTDSNYV AKAYNEELDV WASNGFVNNR KKPLKHISKW KSVADLKRLR PDVVVTHEPG 730 740 750 760 770 780 HQKLDSSPHA YGNNLADQLA TQASFKVHMT KNPKLDIEQI KAIQACQNNE RLPVGYPKQY 790 800 810 820 830 840 TYELQNNKCM VLRKDGWREI PPSRERYKLI KEAHNISHAG REAVLLKIQE NYWWPKMKKD 850 860 870 880 890 900 ISSFLSTCNV CKMVNPLNLK PISPQAIVHP TKPFDKFYMD YIGPLPPSEG YVHVLVVVDA 910 920 930 940 950 960 ATGFTWLYPT KAQTSKATIK VLNHLTGLAI PKVLHSDQGS AFTSEEFAQW AKERNIQLEF 970 980 990 1000 1010 1020 STPYHPQSSG KVERKNSEIK KLLTKLLVGR PLKWYNLISS VQLALNNTHV VSTKYTPHQL 1030 1040 1050 1060 1070 1080 MFGIDCNLPF ANKDTLDWTR EEELALLQEI RESLQHPVQP PTCSGWSPYV GQLVQERVYR 1090 1100 1110 1120 1130 1140 PSQLRPKWRK PTKVLEILNP RTVIIVDHLG QRKSVSIDNL KPTAHQHNGT RTCDDPEGMD 1150 GMECSQTTTE TSVDSS

References

[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: 9261397] [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: 9601510] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate FUV.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ223851 Genomic RNA. Translation: CAA11581.1. Y08851 Genomic DNA. Translation: CAA70075.1.
RefSeq	NP_056914.1. NC_001871.1.
3D structure databases
ProteinModelPortal	O93209.
ModBase	Search...
Protein family/group databases
MEROPS	A09.001.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	2717067.
Family and domain databases
InterPro	IPR001584. Integrase_cat-core. IPR001641. Peptidase_A9_cat. IPR012337. RNaseH-like_dom. IPR002156. RNaseH_domain. IPR000477. RVT. [Graphical view]
Pfam	PF00075. RNase_H. 1 hit. PF00665. rve. 1 hit. PF00078. RVT_1. 1 hit. PF03539. Spuma_A9PTase. 1 hit. [Graphical view]
PRINTS	PR00920. SPUMVIRPTASE.
ProDom	PD013079. Peptidase_A9_cat. 1 hit. [Graphical view] [Entries sharing at least one domain]
SUPFAM	SSF53098. RNaseH_fold. 2 hits.
PROSITE	PS50175. ASP_PROT_RETROV. False negative. PS00141. ASP_PROTEASE. False negative. PS51531. FV_PR. 1 hit. PS50994. INTEGRASE. 1 hit. PS50879. RNASE_H. 1 hit. PS50878. RT_POL. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

POL_FFV

Accession

Primary (citable) accession number: O93209

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2006
Last sequence update:	November 1, 1998
Last modified:	January 25, 2012
This is version 70 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program