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Q2F7J0

- POL_XMRV4

UniProt

Q2F7J0 - POL_XMRV4

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Protein

Gag-Pol polyprotein

Gene
gag-pol
Organism
Xenotropic MuLV-related virus (isolate VP42) (XMRV)
Status
Reviewed - Annotation score: 5 out of 5 - Protein inferred from homologyi

Functioni

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 activityi

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

Cofactori

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei129 – 1302Cleavage; by viral protease p14 By similarity
Sitei213 – 2142Cleavage; by viral protease p14 By similarity
Sitei476 – 4772Cleavage; by viral protease p14 By similarity
Sitei532 – 5332Cleavage; by viral protease p14 By similarity
Active sitei564 – 5641Protease; shared with dimeric partner By similarity
Sitei657 – 6582Cleavage; by viral protease p14 By similarity
Metal bindingi807 – 8071Magnesium; catalytic; for reverse transcriptase activity By similarity
Metal bindingi881 – 8811Magnesium; catalytic; for reverse transcriptase activity By similarity
Metal bindingi882 – 8821Magnesium; catalytic; for reverse transcriptase activity By similarity
Metal bindingi1181 – 11811Magnesium; for RNase H activity By similarity
Metal bindingi1219 – 12191Magnesium; for RNase H activity By similarity
Metal bindingi1240 – 12401Magnesium; for RNase H activity By similarity
Metal bindingi1310 – 13101Magnesium; for RNase H activity By similarity
Sitei1328 – 13292Cleavage; by viral protease p14 By similarity
Metal bindingi1453 – 14531Magnesium; catalytic; for integrase activity By similarity
Metal bindingi1512 – 15121Magnesium; catalytic; for integrase activity By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri500 – 51718CCHC-typeAdd
BLAST

GO - Molecular functioni

  1. aspartic-type endopeptidase activity Source: UniProtKB-KW
  2. DNA binding Source: UniProtKB-KW
  3. DNA-directed DNA polymerase activity Source: UniProtKB-KW
  4. RNA binding Source: UniProtKB-KW
  5. RNA-directed DNA polymerase activity Source: UniProtKB-KW
  6. RNA-DNA hybrid ribonuclease activity Source: UniProtKB-EC
  7. structural constituent of virion Source: UniProtKB-KW
  8. zinc ion binding Source: InterPro

GO - Biological processi

  1. DNA integration Source: UniProtKB-KW
  2. DNA recombination Source: UniProtKB-KW
  3. establishment of integrated proviral latency Source: UniProtKB-KW
  4. viral entry into host cell Source: UniProtKB-KW
  5. virion assembly Source: InterPro
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, Virus entry into host cell

Keywords - Ligandi

DNA-binding, Magnesium, Metal-binding, RNA-binding, Viral nucleoprotein, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Gag-Pol polyprotein
Short name:
Pr180gag-pol
Cleaved into the following 7 chains:
Matrix protein p15
Short name:
MA
Alternative name(s):
pp12
Capsid protein p30
Short name:
CA
Nucleocapsid protein p10
Short name:
NC-pol
Protease p14 (EC:3.4.23.-)
Short name:
PR
Integrase p46
Short name:
IN
Gene namesi
Name:gag-pol
OrganismiXenotropic MuLV-related virus (isolate VP42) (XMRV)
Taxonomic identifieri356664 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeGammaretrovirusunclassified Gammaretrovirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000008602: Genome

Subcellular locationi

Chain Matrix protein p15 : Virion Reviewed prediction
Chain Capsid protein p30 : Virion Reviewed prediction

GO - Cellular componenti

  1. host cell plasma membrane Source: UniProtKB-SubCell
  2. membrane Source: UniProtKB-KW
  3. viral nucleocapsid Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Capsid protein, Host cell membrane, Host membrane, Membrane, Viral matrix protein, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed; by host By similarity
Chaini2 – 17331732Gag-Pol polyproteinPRO_0000390860Add
BLAST
Chaini2 – 129128Matrix protein p15 By similarityPRO_0000390861Add
BLAST
Chaini130 – 21384RNA-binding phosphoprotein p12 By similarityPRO_0000390862Add
BLAST
Chaini214 – 476263Capsid protein p30 By similarityPRO_0000390863Add
BLAST
Chaini477 – 53256Nucleocapsid protein p10 By similarityPRO_0000390864Add
BLAST
Chaini533 – 657125Protease p14 By similarityPRO_0000390865Add
BLAST
Chaini658 – 1328671Reverse transcriptase/ribonuclease H p80 By similarityPRO_0000390866Add
BLAST
Chaini1329 – 1733405Integrase p46 By similarityPRO_0000390867Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine; by host By similarity
Modified residuei190 – 1901Phosphoserine; by host By similarity

Post-translational modificationi

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.

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

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.

Protein-protein interaction databases

MINTiMINT-8206315.

Structurei

3D structure databases

ProteinModelPortaliQ2F7J0.
SMRiQ2F7J0. Positions 2-98, 214-345, 350-380, 477-532, 681-1131, 1160-1325.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini559 – 62971Peptidase A2Add
BLAST
Domaini739 – 930192Reverse transcriptaseAdd
BLAST
Domaini1172 – 1318147RNase HAdd
BLAST
Domaini1442 – 1600159Integrase catalyticAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili436 – 47641 Reviewed predictionAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi109 – 1124PTAP/PSAP motif
Motifi128 – 1325LYPX(n)L motif
Motifi161 – 1644PPXY motif

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi71 – 191121Pro-richAdd
BLAST
Compositional biasi71 – 16898Pro-richAdd
BLAST

Domaini

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.

Sequence similaritiesi

Contains 1 RNase H domain.

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri500 – 51718CCHC-typeAdd
BLAST

Keywords - Domaini

Coiled coil, Zinc-finger

Family and domain databases

Gene3Di1.10.150.180. 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.
InterProiIPR001969. 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]
PfamiPF01140. 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]
SMARTiSM00343. ZnF_C2HC. 1 hit.
[Graphical view]
SUPFAMiSSF47836. SSF47836. 1 hit.
SSF47943. SSF47943. 1 hit.
SSF50630. SSF50630. 1 hit.
SSF53098. SSF53098. 2 hits.
SSF57756. SSF57756. 1 hit.
PROSITEiPS50175. 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]

Sequencei

Sequence statusi: Complete.

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

Q2F7J0-1 [UniParc]FASTAAdd to Basket

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MGQTVTTPLS LTLQHWGDVQ RIASNQSVDV KKRRWVTFCS AEWPTFNVGW     50
PQDGTFNLGI ISQVKSRVFC PGPHGHPDQV PYIVTWEALA YDPPPWVKPF 100
VSPKPPPLPT APVLPPGPSA QPPSRSALYP ALTPSIKSKP PKPQVLPDSG 150
GPLIDLLTED PPPYGAQPSS SARENNEEEA ATTSEVSPPS PMVSRLRGRR 200
DPPAADSTTS QAFPLRMGGD GQLQYWPFSS SDLYNWKNNN PSFSEDPGKL 250
TALIESVLIT HQPTWDDCQQ LLGTLLTGEE KQRVLLEARK AVRGNDGRPT 300
QLPNEVNAAF PLERPDWGYT TTEGRNHLVL YRQLLLAGLQ NAGRSPTNLA 350
KVKGITQGPN ESPSAFLERL KEAYRRYTPY DPEDPGQETN VSMSFIWQSA 400
PDIGRKLERL EDLKSKTLGD LVREAEKIFN KRETPEEREE RIRREIEEKE 450
ERRRAEDEQR ERERDRRRHR EMSKLLATVV IGQRQDRQGG ERRRPQLDKD 500
QCAYCKEKGH WAKDCPKKPR GPRGPRPQTS LLTLGDXGGQ GQEPPPEPRI 550
TLKVGGQPVT FLVDTGAQHS VLTQNPGPLS DKSAWVQGAT GGKRYRWTTD 600
RKVHLATGKV THSFLHVPDC PYPLLGRDLL TKLKAQIHFE GSGAQVVGPM 650
GQPLQVLTLN IEDEYRLHET SKEPDVPLGS TWLSDFPQAW AETGGMGLAV 700
RQAPLIIPLK ATSTPVSIKQ YPMSQEARLG IKPHIQRLLD QGILVPCQSP 750
WNTPLLPVKK PGTNDYRPVQ DLREVNKRVE DIHPTVPNPY NLLSGLPPSH 800
QWYTVLDLKD AFFCLRLHPT SQPLFAFEWR DPEMGISGQL TWTRLPQGFK 850
NSPTLFDEAL HRDLADFRIQ HPDLILLQYV DDLLLAATSE QDCQRGTRAL 900
LQTLGNLGYR ASAKKAQICQ KQVKYLGYLL KEGQRWLTEA RKETVMGQPT 950
PKTPRQLREF LGTAGFCRLW IPGFAEMAAP LYPLTKTGTL FNWGPDQQKA 1000
YQEIKQALLT APALGLPDLT KPFELFVDEK QGYAKGVLTQ KLGPWRRPVA 1050
YLSKKLDPVA AGWPPCLRMV AAIAVLTKDA GKLTMGQPLV ILAPHAVEAL 1100
VKQPPDRWLS NARMTHYQAM LLDTDRVQFG PVVALNPATL LPLPEKEAPH 1150
DCLEILAETH GTRPDLTDQP IPDADYTWYT DGGSFLQEGQ RRAGAAVTTE 1200
TEVIWGGVLP AGTSAQRAEL IALTQALKMA EGKKLNVYTD SRYAFATAHV 1250
HGEIYRRRGL LTSEGREIKN KNEILALLKA LFLPKRLSII HCPGHQKGNS 1300
AEARGNRMAD QAAREAAMKA VLETSTLLIE DSTPYTPPHF HYTETDLKRL 1350
RELGATYNQT KGYWVLQGKP VMPDQSVFEL LDSLHRLTHL SPQKMKALLD 1400
REESPYYMLN RDRTIQYVTE TCTACAQVNA SKAKIGAGVR VRGHRPGTHW 1450
EVDFTEVKPG LYGYKYLLVF VDTFSGWVEA FPTKRETAKV VSKKLLEDIF 1500
PRFGMPQVLG SDNGPAFASQ VSQSVADLLG IDWKLHCAYR PQSSGQVERM 1550
NRTIKETLTK LTLASGTRDW VLLLPLALYR ARNTPGPHGL TPYEILYGAP 1600
PPLVNFHDPE MSKLTNSPSL QAHLQALQAV QQEVWKPLAA AYQDQLDQPV 1650
IPHPFRVGDA VWVRRHQTKN LEPRWKGPYT VLLTTPTALK VDGISAWIHA 1700
AHVKAATTPP AGTAWKVQRS QNPLKIRLTR GAP 1733
Length:1,733
Mass (Da):193,702
Last modified:March 21, 2006 - v1
Checksum:i4208EFFD6F95FA25
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
DQ241302 Genomic RNA. Translation: ABB83228.1.

Keywords - Coding sequence diversityi

RNA suppression of termination

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
DQ241302 Genomic RNA. Translation: ABB83228.1 .

3D structure databases

ProteinModelPortali Q2F7J0.
SMRi Q2F7J0. Positions 2-98, 214-345, 350-380, 477-532, 681-1131, 1160-1325.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

MINTi MINT-8206315.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Family and domain databases

Gene3Di 1.10.150.180. 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.
InterProi IPR001969. 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 ]
Pfami PF01140. 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 ]
SMARTi SM00343. ZnF_C2HC. 1 hit.
[Graphical view ]
SUPFAMi SSF47836. SSF47836. 1 hit.
SSF47943. SSF47943. 1 hit.
SSF50630. SSF50630. 1 hit.
SSF53098. SSF53098. 2 hits.
SSF57756. SSF57756. 1 hit.
PROSITEi PS50175. 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 ]
ProtoNeti Search...

Publicationsi

  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].

Entry informationi

Entry nameiPOL_XMRV4
AccessioniPrimary (citable) accession number: Q2F7J0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 19, 2010
Last sequence update: March 21, 2006
Last modified: May 14, 2014
This is version 71 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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.

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

External Data

Dasty 3

Similar proteinsi