P14350 (POL_FOAMV) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 120. History...
Names and origin
|Protein names||Recommended name:|
Cleaved into the following 4 chains:
|Organism||Human spumaretrovirus (SFVcpz(hu)) (Human foamy virus) [Complete proteome]|
|Taxonomic identifier||11963 [NCBI]|
|Taxonomic lineage||Viruses › Retro-transcribing viruses › Retroviridae › Spumaretrovirinae › Spumavirus ›|
|Virus host||Homo sapiens (Human) [TaxID: 9606]|
|Sequence length||1143 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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.
Endonucleolytic cleavage to 5'-phosphomonoester.
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
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.
The protease is a homodimer, whose active site consists of two apposed aspartic acid residues By similarity.
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.
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. Ref.8
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.
Contains 1 integrase catalytic domain.
Contains 1 peptidase A9 domain.
Contains 1 reverse transcriptase domain.
Contains 1 RNase H domain.
The sequence AAA66556.1 differs from that shown. Reason: Erroneous initiation.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 1143||1143||Pro-Pol polyprotein||PRO_0000125483|
|Chain||1 – 751||751||Protease/Reverse transcriptase/ribonuclease H||PRO_0000245443|
|Chain||1 – 596||596||Protease/Reverse transcriptase||PRO_0000245444|
|Chain||597 – 751||155||Ribonuclease H||PRO_0000245445|
|Chain||752 – 1143||392||Integrase||PRO_0000245446|
|Domain||1 – 143||143||Peptidase A9|
|Domain||198 – 363||166||Reverse transcriptase|
|Domain||590 – 748||159||RNase H|
|Domain||868 – 1024||157||Integrase catalytic|
|Active site||24||1||For protease activity Probable|
|Metal binding||252||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||314||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||315||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||599||1||Magnesium; catalytic; for RNase H activity Probable|
|Metal binding||646||1||Magnesium; catalytic; for RNase H activity By similarity|
|Metal binding||669||1||Magnesium; catalytic; for RNase H activity By similarity|
|Metal binding||740||1||Magnesium; catalytic; for RNase H activity By similarity|
|Metal binding||874||1||Magnesium; catalytic; for integrase activity By similarity|
|Metal binding||936||1||Magnesium; catalytic; for integrase activity By similarity|
|Site||596 – 597||2||Cleavage; by viral protease; partial|
|Site||751 – 752||2||Cleavage; by viral protease|
|Mutagenesis||24||1||D → A: Complete loss of Gag processing and of Pol processing. Particles are non-infectious. Ref.5|
|Mutagenesis||25||1||S → T: No effect on polyprotein processing and viral replication. Ref.5|
|Mutagenesis||152||1||P → G: No effect on RT or RNase H activities. Ref.6|
|Mutagenesis||169||1||P → G: 30% loss of RT activity. Ref.6|
|Mutagenesis||193||1||P → G: 40% loss of RT activity. Ref.6|
|Mutagenesis||599||1||D → A: 95% loss of RNase H activity. Ref.6|
|Mutagenesis||672||1||Y → F: 50% loss of RNase H activity. Ref.6|
Helix Strand Turn
|Beta strand||593 – 603||11|
|Beta strand||613 – 621||9|
|Beta strand||624 – 626||3|
|Beta strand||629 – 639||11|
|Helix||642 – 659||18|
|Beta strand||660 – 662||3|
|Beta strand||664 – 669||6|
|Helix||671 – 678||8|
|Helix||680 – 686||7|
|Beta strand||693 – 695||3|
|Helix||700 – 712||13|
|Beta strand||717 – 720||4|
|Beta strand||723 – 725||3|
|Beta strand||727 – 729||3|
|Helix||731 – 749||19|
|Helix||760 – 767||8|
|Beta strand||773 – 775||3|
|Beta strand||777 – 779||3|
|Beta strand||781 – 784||4|
|Beta strand||787 – 792||6|
|Beta strand||795 – 798||4|
|Helix||802 – 804||3|
|Helix||805 – 814||10|
|Turn||815 – 817||3|
|Helix||820 – 828||9|
|Helix||836 – 844||9|
|Helix||848 – 853||6|
|Beta strand||858 – 860||3|
|Beta strand||874 – 881||8|
|Beta strand||892 – 898||7|
|Turn||899 – 901||3|
|Beta strand||904 – 912||9|
|Helix||914 – 924||11|
|Turn||925 – 927||3|
|Beta strand||931 – 935||5|
|Helix||939 – 942||4|
|Helix||944 – 953||10|
|Beta strand||956 – 959||4|
|Helix||965 – 968||4|
|Helix||970 – 987||18|
|Turn||990 – 996||7|
|Helix||997 – 1005||9|
|Turn||1010 – 1012||3|
|Helix||1016 – 1021||6|
|Beta strand||1023 – 1025||3|
|Beta strand||1028 – 1030||3|
|Turn||1033 – 1036||4|
|Helix||1040 – 1054||15|
|Beta strand||1073 – 1077||5|
|Beta strand||1092 – 1099||8|
|Beta strand||1102 – 1106||5|
|Beta strand||1108 – 1110||3|
|Beta strand||1112 – 1116||5|
|Helix||1117 – 1119||3|
|Beta strand||1120 – 1122||3|
Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], SEQUENCE REVISION.
|||"Long terminal repeat U3-length polymorphism of human foamy virus."|
Schmidt M., Herchenrder O., Heeney J.L., Rethwilm A.
Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|||"Analysis of the primary structure of the long terminal repeat and the gag and pol genes of the human spumaretrovirus."|
Maurer B., Bannert H., Darai G., Fluegel R.M.
J. Virol. 62:1590-1597(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-742.
|||"Nucleotide sequence analysis of the env gene and its flanking regions of the human spumaretrovirus reveals two novel genes."|
Fluegel R.M., Rethwilm A., Maurer B., Darai G.
EMBO J. 6:2077-2084(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 741-886.
|||"Active foamy virus proteinase is essential for virus infectivity but not for formation of a Pol polyprotein."|
Konvalinka J., Loechelt M., Zentgraf H., Fluegel R.M., Kraeusslich H.-G.
J. Virol. 69:7264-7268(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVE SITE OF PROTEASE, MUTAGENESIS OF ASP-24 AND SER-25.
|||"Mutational analysis of the reverse transcriptase and ribonuclease H domains of the human foamy virus."|
Kogel D., Aboud M., Fluegel R.M.
Nucleic Acids Res. 23:2621-2625(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF PRO-152; PRO-169; PRO-193; ASP-599 AND TYR-672.
|||"The human foamy virus pol gene is expressed as a Pro-Pol polyprotein and not as a Gag-Pol fusion protein."|
Loechelt M., Fluegel R.M.
J. Virol. 70:1033-1040(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF POLYPROTEIN.
|||"Molecular characterization of proteolytic processing of the Pol proteins of human foamy virus reveals novel features of the viral protease."|
Pfrepper K.-I., Rackwitz H.R., Schnoelzer M., Heid H., Loechelt M., Fluegel R.M.
J. Virol. 72:7648-7652(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
|||"Primate foamy virus Pol proteins are imported into the nucleus."|
Imrich H., Heinkelein M., Herchenroder O., Rethwilm A.
J. Gen. Virol. 81:2941-2947(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
Strain: Isolate HSRV2.
|||"Biphasic DNA synthesis in spumaviruses."|
Delelis O., Saib A., Sonigo P.
J. Virol. 77:8141-8146(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF REVERSE TRANSCRIPTASE.
|||"Foamy virus integration."|
Juretzek T., Holm T., Gartner K., Kanzler S., Lindemann D., Herchenroder O., Picard-Maureau M., Rammling M., Heinkelein M., Rethwilm A.
J. Virol. 78:2472-2477(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF INTEGRASE.
|||"Proteolytic processing of foamy virus Gag and Pol proteins."|
Fluegel R.M., Pfrepper K.-I.
Curr. Top. Microbiol. Immunol. 277:63-88(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"Foamy viruses-a world apart."|
Delelis O., Lehmann-Che J., Saib A.
Curr. Opin. Microbiol. 7:400-406(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|+||Additional computationally mapped references.|
|U21247 Genomic RNA. Translation: AAB48112.1.|
Y07723 Genomic DNA. Translation: CAA68997.1.
Y07724 Genomic DNA. Translation: CAA68999.1.
Y07725 Genomic DNA. Translation: CAA69003.1.
M19427 Genomic RNA. Translation: AAA66556.1. Different initiation.
M54978 Genomic RNA. Translation: AAA46122.1. Frameshift.
3D structure databases
|SMR||P14350. Positions 8-98. |
Protein-protein interaction databases
Protein family/group databases
Protocols and materials databases
Family and domain databases
|Gene3D||3.30.420.10. 2 hits. |
|InterPro||IPR001584. Integrase_cat-core. |
|Pfam||PF00075. RNase_H. 1 hit. |
PF00665. rve. 1 hit.
PF00078. RVT_1. 1 hit.
PF03539. Spuma_A9PTase. 1 hit.
|PRINTS||PR00920. SPUMVIRPTASE. |
|ProDom||PD013079. Peptidase_A9_cat. 1 hit. |
[Graphical view] [Entries sharing at least one domain]
|SUPFAM||SSF53098. SSF53098. 2 hits. |
|PROSITE||PS51531. FV_PR. 1 hit. |
PS50994. INTEGRASE. 1 hit.
PS50879. RNASE_H. 1 hit.
PS50878. RT_POL. 1 hit.
|Accession||Primary (citable) accession number: P14350|
Secondary accession number(s): O12528 Q98835
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|