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Protein

Pro-Pol polyprotein

Gene

pol

Organism
Simian foamy virus type 1 (SFVmac) (SFV-1)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.1 Publication

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)DescriptionActionsGraphical viewLength
Active sitei24For protease activityPROSITE-ProRule annotation1
Metal bindingi252Magnesium; catalytic; for reverse transcriptase activityBy similarity1
Metal bindingi314Magnesium; catalytic; for reverse transcriptase activityBy similarity1
Metal bindingi315Magnesium; catalytic; for reverse transcriptase activityBy similarity1
Metal bindingi599Magnesium; catalytic; for RNase H activityBy similarity1
Metal bindingi646Magnesium; catalytic; for RNase H activityBy similarity1
Metal bindingi669Magnesium; catalytic; for RNase H activityBy similarity1
Metal bindingi740Magnesium; catalytic; for RNase H activityBy similarity1
Metal bindingi873Magnesium; catalytic; for integrase activityBy similarity1
Metal bindingi935Magnesium; catalytic; for integrase activityBy similarity1

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

Enzyme and pathway databases

BRENDAi3.4.23.B11. 8746.

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
OrganismiSimian foamy virus type 1 (SFVmac) (SFV-1)
Taxonomic identifieri338478 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeSpumaretrovirinaeSpumavirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Macaca (macaques) [TaxID: 9539]
Proteomesi
  • UP000007216 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)DescriptionActionsGraphical viewLength
ChainiPRO_00001254841 – 1149Pro-Pol polyproteinAdd BLAST1149
ChainiPRO_00002454471 – 751Protease/Reverse transcriptase/ribonuclease HBy similarityAdd BLAST751
ChainiPRO_00002454481 – 596Protease/Reverse transcriptaseBy similarityAdd BLAST596
ChainiPRO_0000245449597 – 751Ribonuclease HBy similarityAdd BLAST155
ChainiPRO_0000245450752 – 1149IntegraseBy similarityAdd BLAST398

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei596 – 597Cleavage; by viral protease; partialBy similarity2
Sitei751 – 752Cleavage; by viral proteaseBy similarity2

Interactioni

Subunit structurei

The protease is a homodimer, whose active site consists of two apposed aspartic acid residues.PROSITE-ProRule annotation

Structurei

Secondary structure

11149
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi10 – 14Combined sources5
Beta strandi17 – 23Combined sources7
Beta strandi28 – 33Combined sources6
Helixi34 – 36Combined sources3
Turni37 – 39Combined sources3
Beta strandi43 – 49Combined sources7
Beta strandi54 – 68Combined sources15
Beta strandi70 – 85Combined sources16
Turni87 – 89Combined sources3
Helixi91 – 94Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JYSNMR-A1-101[»]
ProteinModelPortaliP23074.
SMRiP23074.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23074.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 143Peptidase A9PROSITE-ProRule annotationAdd BLAST143
Domaini186 – 363Reverse transcriptasePROSITE-ProRule annotationAdd BLAST178
Domaini590 – 748RNase HPROSITE-ProRule annotationAdd BLAST159
Domaini867 – 1023Integrase catalyticPROSITE-ProRule annotationAdd BLAST157

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.

P23074-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDPLQLLQPL EAEIKGTKLK AHWDSGATIT CVPEAFLEDE RPIQTMLIKT
60 70 80 90 100
IHGEKQQDVY YLTFKVQGRK VEAEVLASPY DYILLNPSDV PWLMKKPLQL
110 120 130 140 150
TVLVPLHEYQ ERLLQQTALP KEQKELLQKL FLKYDALWQH WENQVGHRRI
160 170 180 190 200
KPHNIATGTL APRPQKQYPI NPKAKPSIQI VIDDLLKQGV LIQQNSTMNT
210 220 230 240 250
PVYPVPKPDG KWRMVLDYRE VNKTIPLIAA QNQHSAGILS SIYRGKYKTT
260 270 280 290 300
LDLTNGFWAH PITPESYWLT AFTWQGKQYC WTRLPQGFLN SPALFTADVV
310 320 330 340 350
DLLKEIPNVQ AYVDDIYISH DDPQEHLEQL EKIFSILLNA GYVVSLKKSE
360 370 380 390 400
IAQREVEFLG FNITKEGRGL TDTFKQKLLN ITPPKDLKQL QSILGLLNFA
410 420 430 440 450
RNFIPNYSEL VKPLYTIVAN ANGKFISWTE DNSNQLQHII SVLNQADNLE
460 470 480 490 500
ERNPETRLII KVNSSPSAGY IRYYNEGSKR PIMYVNYIFS KAEAKFTQTE
510 520 530 540 550
KLLTTMHKGL IKAMDLAMGQ EILVYSPIVS MTKIQRTPLP ERKALPVRWI
560 570 580 590 600
TWMTYLEDPR IQFHYDKSLP ELQQIPNVTE DVIAKTKHPS EFAMVFYTDG
610 620 630 640 650
SAIKHPDVNK SHSAGMGIAQ VQFIPEYKIV HQWSIPLGDH TAQLAEIAAV
660 670 680 690 700
EFACKKALKI SGPVLIVTDS FYVAESANKE LPYWKSNGFL NNKKKPLRHV
710 720 730 740 750
SKWKSIAECL QLKPDIIIMH EKGHQQPMTT LHTEGNNLAD KLATQGSYVV
760 770 780 790 800
HCNTTPSLDA ELDQLLQGHY PPGYPKQYKY TLEENKLIVE RPNGIRIVPP
810 820 830 840 850
KADREKIIST AHNIAHTGRD ATFLKVSSKY WWPNLRKDVV KSIRQCKQCL
860 870 880 890 900
VTNATNLTSP PILRPVKPLK PFDKFYIDYI GPLPPSNGYL HVLVVVDSMT
910 920 930 940 950
GFVWLYPTKA PSTSATVKAL NMLTSIAIPK VLHSDQGAAF TSSTFADWAK
960 970 980 990 1000
EKGIQLEFST PYHPQSSGKV ERKNSDIKRL LTKLLIGRPA KWYDLLPVVQ
1010 1020 1030 1040 1050
LALNNSYSPS SKYTPHQLLF GVDSNTPFAN SDTLDLSREE ELSLLQEIRS
1060 1070 1080 1090 1100
SLHQPTSPPA SSRSWSPSVG QLVQERVARP ASLRPRWHKP TAILEVVNPR
1110 1120 1130 1140
TVIILDHLGN RRTVSVDNLK LTAYQDNGTS NDSGTMALME EDESSTSST
Length:1,149
Mass (Da):130,320
Last modified:July 11, 2006 - v3
Checksum:i013A78E67698ADA3
GO

Sequence cautioni

The sequence AAA47793 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAA41394 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti224T → I in CAA41394 (PubMed:1653483).Curated1
Sequence conflicti898S → G in CAA41394 (PubMed:1653483).Curated1
Sequence conflicti938A → T in CAA41394 (PubMed:1653483).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54482 Genomic DNA. No translation available.
X58484 Genomic DNA. Translation: CAA41394.1. Different initiation.
M33561 Genomic RNA. Translation: AAA47793.1. Different initiation.
PIRiA33562.
S15566.
RefSeqiYP_001961122.1. NC_010819.1.

Genome annotation databases

GeneIDi6386687.
KEGGivg:6386687.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54482 Genomic DNA. No translation available.
X58484 Genomic DNA. Translation: CAA41394.1. Different initiation.
M33561 Genomic RNA. Translation: AAA47793.1. Different initiation.
PIRiA33562.
S15566.
RefSeqiYP_001961122.1. NC_010819.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JYSNMR-A1-101[»]
ProteinModelPortaliP23074.
SMRiP23074.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiA09.001.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi6386687.
KEGGivg:6386687.

Enzyme and pathway databases

BRENDAi3.4.23.B11. 8746.

Miscellaneous databases

EvolutionaryTraceiP23074.

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...

Entry informationi

Entry nameiPOL_SFV1
AccessioniPrimary (citable) accession number: P23074
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: July 11, 2006
Last modified: November 30, 2016
This is version 124 of the entry and version 3 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

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. 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.