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Q2F7J3 (POL_XMRV3) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 70. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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:
Gag-Pol polyprotein

Short name=Pr180gag-pol

Cleaved into the following 7 chains:

  1. Matrix protein p15
    Short name=MA
  2. RNA-binding phosphoprotein p12
    Alternative name(s):
    pp12
  3. Capsid protein p30
    Short name=CA
  4. Nucleocapsid protein p10
    Short name=NC-pol
  5. Protease p14
    Short name=PR
    EC=3.4.23.-
  6. Reverse transcriptase/ribonuclease H p80
    Short name=RT
    EC=2.7.7.49
    EC=2.7.7.7
    EC=3.1.26.4
  7. Integrase p46
    Short name=IN
Gene names
Name:gag-pol
OrganismXenotropic MuLV-related virus (isolate VP35) (XMRV) [Complete proteome]
Taxonomic identifier356663 [NCBI]
Taxonomic lineageVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeGammaretrovirusunclassified Gammaretrovirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length1733 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Matrix protein p15 targets Gag and gag-pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex By similarity.

Capsid protein p30 forms the spherical core of the virion that encapsulates the genomic RNA-nucleocapsid complex By similarity.

Nucleocapsid protein p10 is involved in the packaging and encapsidation of two copies of the genome. Binds with high affinity to conserved UCUG elements within the packaging signal, located near the 5'-end of the genome. This binding is dependent on genome dimerization By similarity.

The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell By similarity.

Reverse transcriptase/ribonuclease H is a multifunctional enzyme that converts the viral dimeric RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays 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 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 primers. 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, leaving recessed CA OH's at the 3' ends. In the second step that requires cell division, the PIC enters cell nucleus. 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. The last step is viral DNA integration into host chromosome By similarity.

Gag-Pol polyprotein plays a role in budding and is processed by the viral protease during virion maturation outside the cell. During budding, it recruits, in a PPXY-dependent or independent manner, Nedd4-like ubiquitin ligases that conjugate ubiquitin molecules to Gag, or to Gag binding host factors. Interaction with HECT ubiquitin ligases probably link the viral protein to the host ESCRT pathway and facilitate release By similarity.

Catalytic activity

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

Endonucleolytic cleavage to 5'-phosphomonoester.

Cofactor

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

Binds 2 magnesium ions for ribonuclease H (RNase H) activity By similarity.

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

Subunit structure

Capsid protein p30 is a homohexamer, that further associates as homomultimer. The virus core is composed of a lattice formed from hexagonal rings, each containing six capsid monomers. The protease is a homodimer, whose active site consists of two apposed aspartic acid residues. The reverse transcriptase is a monomer By similarity.

Subcellular location

Gag-Pol polyprotein: Host cell membrane; Lipid-anchor Potential.

Matrix protein p15: Virion Potential.

Capsid protein p30: Virion Potential.

Nucleocapsid protein p10: Virion Potential.

Domain

Late-budding domains (L domains) are short sequence motifs essential for viral particle release. They can occur individually or in close proximity within structural proteins. They interacts with sorting cellular proteins of the multivesicular body (MVB) pathway. Most of these proteins are class E vacuolar protein sorting factors belonging to ESCRT-I, ESCRT-II or ESCRT-III complexes. RNA-binding phosphoprotein p12 contains one L domain: a PPXY motif which potentially interacts with the WW domain 3 of NEDD4 E3 ubiquitin ligase. PPXY motif is essential for virus egress. Matrix protein p15 contains one L domain: a PTAP/PSAP motif, which potentially interacts with the UEV domain of TSG101. The junction between the matrix protein p15 and RNA-binding phosphoprotein p12 also contains one L domain: a LYPX(n)L motif which potentially interacts with PDCD6IP. Both PSAP and LYPX(n)L domains might play little to no role in budding and possibly drive residual virus release. contains By similarity.

Post-translational modification

Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation By similarity.

Capsid protein p30 is sumoylated; which is required for virus replication.

RNA-binding phosphoprotein p12 is phosphorylated on serine residues By similarity.

Miscellaneous

This protein is translated as a gag-pol fusion protein by episodic readthrough of the gag protein termination codon. Readthrough of the terminator codon TAG occurs between the codons for 536-Asp and 538-Gly By similarity.

The nucleocapsid protein p10 released from Pol polyprotein (NC-pol) is a few amino acids shorter than the nucleocapsid protein p10 released from Gag polyprotein (NC-gag) By similarity.

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 swiching 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 By similarity.

Sequence similarities

Contains 1 CCHC-type zinc finger.

Contains 1 integrase catalytic domain.

Contains 1 integrase-type DNA-binding 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 componentCapsid protein
Host cell membrane
Host membrane
Membrane
Viral matrix protein
Virion
   Coding sequence diversityRNA suppression of termination
   DomainCoiled coil
Zinc-finger
   LigandDNA-binding
Magnesium
Metal-binding
RNA-binding
Viral nucleoprotein
Zinc
   Molecular functionAspartyl protease
DNA-directed DNA polymerase
Endonuclease
Hydrolase
Nuclease
Nucleotidyltransferase
Protease
RNA-directed DNA polymerase
Transferase
   PTMLipoprotein
Myristate
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete 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

virion assembly

Inferred from electronic annotation. Source: InterPro

   Cellular_componenthost cell plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from electronic annotation. Source: UniProtKB-KW

viral nucleocapsid

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA-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

structural constituent of virion

Inferred from electronic annotation. Source: UniProtKB-KW

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed; by host By similarity
Chain2 – 17331732Gag-Pol polyprotein By similarity
PRO_0000390852
Chain2 – 129128Matrix protein p15 By similarity
PRO_0000390853
Chain130 – 21384RNA-binding phosphoprotein p12 By similarity
PRO_0000390854
Chain214 – 476263Capsid protein p30 By similarity
PRO_0000390855
Chain477 – 53256Nucleocapsid protein p10 By similarity
PRO_0000390856
Chain533 – 657125Protease p14 By similarity
PRO_0000390857
Chain658 – 1328671Reverse transcriptase/ribonuclease H p80 By similarity
PRO_0000390858
Chain1329 – 1733405Integrase p46 By similarity
PRO_0000390859

Regions

Domain559 – 62971Peptidase A2
Domain739 – 930192Reverse transcriptase
Domain1172 – 1318147RNase H
Domain1442 – 1600159Integrase catalytic
Zinc finger500 – 51718CCHC-type
Coiled coil436 – 47641 Potential
Motif109 – 1124PTAP/PSAP motif
Motif128 – 1325LYPX(n)L motif
Motif161 – 1644PPXY motif
Compositional bias71 – 191121Pro-rich

Sites

Active site5641Protease; shared with dimeric partner By similarity
Metal binding8071Magnesium; catalytic; for reverse transcriptase activity By similarity
Metal binding8811Magnesium; catalytic; for reverse transcriptase activity By similarity
Metal binding8821Magnesium; catalytic; for reverse transcriptase activity By similarity
Metal binding11811Magnesium; for RNase H activity By similarity
Metal binding12191Magnesium; for RNase H activity By similarity
Metal binding12401Magnesium; for RNase H activity By similarity
Metal binding13101Magnesium; for RNase H activity By similarity
Metal binding14531Magnesium; catalytic; for integrase activity By similarity
Metal binding15121Magnesium; catalytic; for integrase activity By similarity
Site129 – 1302Cleavage; by viral protease p14 By similarity
Site213 – 2142Cleavage; by viral protease p14 By similarity
Site476 – 4772Cleavage; by viral protease p14 By similarity
Site532 – 5332Cleavage; by viral protease p14 By similarity
Site657 – 6582Cleavage; by viral protease p14 By similarity
Site1328 – 13292Cleavage; by viral protease p14 By similarity

Amino acid modifications

Modified residue1901Phosphoserine; by host By similarity
Lipidation21N-myristoyl glycine; by host By similarity

Secondary structure

.......................... 1733
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q2F7J3 [UniParc].

Last modified March 21, 2006. Version 1.
Checksum: 35B226FA584B5122

FASTA1,733193,803
        10         20         30         40         50         60 
MGQTVTTPLS LTLQHWGDVQ RIASNQSVDV KKRRWVTFCS AEWPTFNVGW PQDGTFNLGV 

        70         80         90        100        110        120 
ISQVKSRVFC PGPHGHPDQV PYIVTWEALA YDPPPWVKPF VSPKPPPLPT APVLPPGPSA 

       130        140        150        160        170        180 
QPPSRSALYP ALTLSIKSKP PKPQVLPDSG GPLIDLLTED PPPYGVQPSS SARENNEEEA 

       190        200        210        220        230        240 
ATTSEVSPPS PMVSRLRGRR DPPAADSTTS QAFPLRMGGD GQLQYWPFSS SDLYNWKNNN 

       250        260        270        280        290        300 
PSFSEDPGKL TALIESVLIT HQPTWDDCQQ LLGTLLTGEE KQRVLLEAGK AVRGNDGRPT 

       310        320        330        340        350        360 
QLPNEVNAAF PLERPDWDYT TTEGRNHLVL YRQLLLAGLQ NAGRSPTNLA KVKGITQGPN 

       370        380        390        400        410        420 
ESPSAFLERL KEAYRRYTPY DPEDPGQETN VSMSFIWQSA PDIGRKLERL EDLKSKTLGD 

       430        440        450        460        470        480 
LVREAEKIFN KRETPEEREE RIRREIEEKE ERRRAEDEQR ERERDRRRHR EMSKLLATVV 

       490        500        510        520        530        540 
IGQRQDRQGG ERRRPQLDKD QCAYCKEKGH WAKDCPKKPR GPRGPRPQTS LLTLGDXGGQ 

       550        560        570        580        590        600 
GQEPPPEPRI TLKVGGQPVT FLVDTGAQHS VLTQNPGPLS DKSAWVQGAT GGKRYRWTTD 

       610        620        630        640        650        660 
RKVHLATGKV THSFLHVPDC PYPLLGRDLL TKLKAQIHFE GSGAQVVGPM GQPLQVLTLN 

       670        680        690        700        710        720 
IENKYRLHET SKEPDVPLGS TWLSDFPQAW AETGGMGLAV RQAPLIIPLK ATSTPVSIKQ 

       730        740        750        760        770        780 
YPMSQEARLG IKPHIQRLLD QGILVPCQSP WNTPLLPVKK PGTNDYRPVQ DLREVNKRVE 

       790        800        810        820        830        840 
DIHPTVPNPY NLLSGLPPSH QWYTVLDLKD AFFCLRLHPT SQPLFAFEWR DPEMGISGQL 

       850        860        870        880        890        900 
TWTRLPQGFK NSPTLFDEAL HRDLADFRIQ HPDLILLQYV DDLLLAATSE QDCQRGTRAL 

       910        920        930        940        950        960 
LQTLGNLGYR ASAKKAQICQ KQVKYLGYLL KEGQRWLTEA RKETVMGQPT PKTPRQLREF 

       970        980        990       1000       1010       1020 
LGTAGFCRLW IPGFAEMAAP LYPLTKTGTL FNWGPDQQKA YQEIKQALLT APALGLPDLT 

      1030       1040       1050       1060       1070       1080 
KPFELFVDEK QGYAKGVLTQ KLGPWRRPVA YLSKKLDPVA AGWPPCLRMV AAIAVLTKDA 

      1090       1100       1110       1120       1130       1140 
GKLTMGQPLV ILAPHAVEAL VKQPPDRWLS NARMTHYQAM LLDTDRVQFG PVVALNPATL 

      1150       1160       1170       1180       1190       1200 
LPLPEKEAPH DCLEILAETH GTRPDLTDQP IPDADYTWYT DGSSFLQEGQ RRAGAAVTTE 

      1210       1220       1230       1240       1250       1260 
TEVIWARALP AGTSAQRAEL IALTQALKMA EGKKLNVYTD SRYAFATAHV HGEIYRRRGL 

      1270       1280       1290       1300       1310       1320 
LTSEGREIKN KNEILALLKA LFLPKRLSII HCPGHQKGNS AEARGNRMAD QAAREAAMKA 

      1330       1340       1350       1360       1370       1380 
VLETSTLLIE DSTPYTPPHF HYTETDLKRL RELGATYNQT KGYWVLQGKP VMPDQSVFEL 

      1390       1400       1410       1420       1430       1440 
LDSLHRLTHP SPQKMKALLD REESPYYMLN RDRTIQYVTE TCTACAQVNA SKAKIGAGVR 

      1450       1460       1470       1480       1490       1500 
VRGHRPGTHW EVDFTEVKPG LYGYKYLLVF VDTFSGWVEA FPTKRETAKV VTKKLLEDIF 

      1510       1520       1530       1540       1550       1560 
PRFGMPQVLG SDNGPAFASQ VSQSVADLLG IDWKLHCAYR PQSSGQVERM NRTIKETLTK 

      1570       1580       1590       1600       1610       1620 
LTLASGTRDW VLLLPLALYR ARNTPGPHGL TPYEILYGAP PPLVNFHDPE MSKLTNSPSL 

      1630       1640       1650       1660       1670       1680 
QAHLQALQAV QQEVWKPLAA AYQDQLDQPV IPHPFRVGDA VWVRRHQTKN LEPRWKGPYT 

      1690       1700       1710       1720       1730 
VLLTTPTALK VDGISAWIHA AHVKAATTPP AGTAWKVQRS QNPLKIRLTR GAP 

« Hide

References

[1]"Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant."
Urisman A., Molinaro R.J., Fischer N., Plummer S.J., Casey G., Klein E.A., Malathi K., Magi-Galluzzi C., Tubbs R.R., Ganem D., Silverman R.H., DeRisi J.L.
PLoS Pathog. 2:E25-E25(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
DQ241301 Genomic RNA. Translation: ABB83225.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3V1OX-ray1.88A1154-1328[»]
3V1QX-ray2.00A1155-1328[»]
3V1RX-ray2.80A1154-1328[»]
ProteinModelPortalQ2F7J3.
SMRQ2F7J3. Positions 2-98, 214-345, 350-380, 477-532, 681-1131, 1160-1325.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D1.10.150.180. 1 hit.
1.10.375.10. 1 hit.
2.40.70.10. 1 hit.
3.30.420.10. 2 hits.
4.10.60.10. 1 hit.
InterProIPR001969. Aspartic_peptidase_AS.
IPR000840. G_retro_matrix_N.
IPR002079. Gag_p12.
IPR003036. Gag_P30.
IPR001584. Integrase_cat-core.
IPR018061. Pept_A2A_retrovirus_sg.
IPR001995. Peptidase_A2_cat.
IPR021109. Peptidase_aspartic_dom.
IPR008919. Retrov_capsid_N.
IPR010999. Retrovr_matrix_N.
IPR012337. RNaseH-like_dom.
IPR002156. RNaseH_domain.
IPR000477. RT_dom.
IPR001878. Znf_CCHC.
[Graphical view]
PfamPF01140. Gag_MA. 1 hit.
PF01141. Gag_p12. 1 hit.
PF02093. Gag_p30. 1 hit.
PF00075. RNase_H. 1 hit.
PF00665. rve. 1 hit.
PF00077. RVP. 1 hit.
PF00078. RVT_1. 1 hit.
[Graphical view]
SMARTSM00343. ZnF_C2HC. 1 hit.
[Graphical view]
SUPFAMSSF47836. SSF47836. 1 hit.
SSF47943. SSF47943. 1 hit.
SSF50630. SSF50630. 1 hit.
SSF53098. SSF53098. 2 hits.
SSF57756. SSF57756. 1 hit.
PROSITEPS50175. ASP_PROT_RETROV. 1 hit.
PS00141. ASP_PROTEASE. 1 hit.
PS50994. INTEGRASE. 1 hit.
PS50879. RNASE_H. 1 hit.
PS50878. RT_POL. 1 hit.
PS50158. ZF_CCHC. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry namePOL_XMRV3
AccessionPrimary (citable) accession number: Q2F7J3
Entry history
Integrated into UniProtKB/Swiss-Prot: January 19, 2010
Last sequence update: March 21, 2006
Last modified: April 16, 2014
This is version 70 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references