Q2F7J0 (POL_XMRV4) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Xenotropic MuLV-related virus (isolate VP42) (XMRV) [Complete proteome]

Taxonomic identifier

356664 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Gammaretrovirus › unclassified Gammaretrovirus › Murine leukemia-related retroviruses › XMRV-related viruses › XMRV

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	1733 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	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 process	DNA integration DNA recombination Viral genome integration Virus entry into host cell
Cellular component	Host cell membrane Host membrane Membrane Viral matrix protein Virion
Coding sequence diversity	RNA suppression of termination
Domain	Coiled coil Zinc-finger
Ligand	DNA-binding Magnesium Metal-binding RNA-binding Viral nucleoprotein Zinc
Molecular function	Aspartyl protease Capsid protein DNA-directed DNA polymerase Endonuclease Hydrolase Nuclease Nucleotidyltransferase Protease RNA-directed DNA polymerase Transferase
PTM	Lipoprotein Myristate Phosphoprotein Ubl conjugation
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 establishment of integrated proviral latency Inferred from electronic annotation. Source: UniProtKB-KW nucleic acid phosphodiester bond hydrolysis Inferred from electronic annotation. Source: GOC 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_component	host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-KW viral capsid Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	DNA 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-directed DNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW aspartic-type endopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW ribonuclease H activity Inferred from electronic annotation. Source: EC structural molecule activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed; by host By similarity
	Chain	2 – 1733	1732	Gag-Pol polyprotein		PRO_0000390860
	Chain	2 – 129	128	Matrix protein p15 By similarity		PRO_0000390861
	Chain	130 – 213	84	RNA-binding phosphoprotein p12 By similarity		PRO_0000390862
	Chain	214 – 476	263	Capsid protein p30 By similarity		PRO_0000390863
	Chain	477 – 532	56	Nucleocapsid protein p10 By similarity		PRO_0000390864
	Chain	533 – 657	125	Protease p14 By similarity		PRO_0000390865
	Chain	658 – 1328	671	Reverse transcriptase/ribonuclease H p80 By similarity		PRO_0000390866
	Chain	1329 – 1733	405	Integrase p46 By similarity		PRO_0000390867
Regions
	Domain	559 – 629	71	Peptidase A2
	Domain	739 – 930	192	Reverse transcriptase
	Domain	1172 – 1318	147	RNase H
	Domain	1442 – 1600	159	Integrase catalytic
	Zinc finger	500 – 517	18	CCHC-type
	Coiled coil	436 – 476	41	Potential
	Motif	109 – 112	4	PTAP/PSAP motif
	Motif	128 – 132	5	LYPX(n)L motif
	Motif	161 – 164	4	PPXY motif
	Compositional bias	71 – 191	121	Pro-rich
	Compositional bias	71 – 168	98	Pro-rich
Sites
	Active site	564	1	Protease; shared with dimeric partner By similarity
	Metal binding	807	1	Magnesium; catalytic; for reverse transcriptase activity By similarity
	Metal binding	881	1	Magnesium; catalytic; for reverse transcriptase activity By similarity
	Metal binding	882	1	Magnesium; catalytic; for reverse transcriptase activity By similarity
	Metal binding	1181	1	Magnesium; for RNase H activity By similarity
	Metal binding	1219	1	Magnesium; for RNase H activity By similarity
	Metal binding	1240	1	Magnesium; for RNase H activity By similarity
	Metal binding	1310	1	Magnesium; for RNase H activity By similarity
	Metal binding	1453	1	Magnesium; catalytic; for integrase activity By similarity
	Metal binding	1512	1	Magnesium; catalytic; for integrase activity By similarity
	Site	129 – 130	2	Cleavage; by viral protease p14 By similarity
	Site	213 – 214	2	Cleavage; by viral protease p14 By similarity
	Site	476 – 477	2	Cleavage; by viral protease p14 By similarity
	Site	532 – 533	2	Cleavage; by viral protease p14 By similarity
	Site	657 – 658	2	Cleavage; by viral protease p14 By similarity
	Site	1328 – 1329	2	Cleavage; by viral protease p14 By similarity
Amino acid modifications
	Modified residue	190	1	Phosphoserine; by host By similarity
	Lipidation	2	1	N-myristoyl glycine; by host By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q2F7J0 [UniParc]. Last modified March 21, 2006. Version 1. Checksum: 4208EFFD6F95FA25	FASTA	1,733	193,702
	10 20 30 40 50 60 MGQTVTTPLS LTLQHWGDVQ RIASNQSVDV KKRRWVTFCS AEWPTFNVGW PQDGTFNLGI 70 80 90 100 110 120 ISQVKSRVFC PGPHGHPDQV PYIVTWEALA YDPPPWVKPF VSPKPPPLPT APVLPPGPSA 130 140 150 160 170 180 QPPSRSALYP ALTPSIKSKP PKPQVLPDSG GPLIDLLTED PPPYGAQPSS SARENNEEEA 190 200 210 220 230 240 ATTSEVSPPS PMVSRLRGRR DPPAADSTTS QAFPLRMGGD GQLQYWPFSS SDLYNWKNNN 250 260 270 280 290 300 PSFSEDPGKL TALIESVLIT HQPTWDDCQQ LLGTLLTGEE KQRVLLEARK AVRGNDGRPT 310 320 330 340 350 360 QLPNEVNAAF PLERPDWGYT 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 IEDEYRLHET 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 DGGSFLQEGQ RRAGAAVTTE 1210 1220 1230 1240 1250 1260 TEVIWGGVLP 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 LDSLHRLTHL SPQKMKALLD REESPYYMLN RDRTIQYVTE TCTACAQVNA SKAKIGAGVR 1450 1460 1470 1480 1490 1500 VRGHRPGTHW EVDFTEVKPG LYGYKYLLVF VDTFSGWVEA FPTKRETAKV VSKKLLEDIF 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

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].

Cross-references

Sequence databases
EMBL GenBank DDBJ	DQ241302 Genomic RNA. Translation: ABB83228.1.
3D structure databases
ProteinModelPortal	Q2F7J0.
SMR	Q2F7J0. Positions 2-98, 214-345, 350-380, 477-532, 681-1131, 1160-1325.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
Gene3D	1.10.150.180. 1 hit. 1.10.375.10. 1 hit. 2.40.70.10. 1 hit. 4.10.60.10. 1 hit.
InterPro	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. IPR001969. Peptidase_aspartic_AS. IPR008919. Retrov_capsid_N. IPR010999. Retrovr_matrix_N. IPR012337. RNaseH-like_dom. IPR002156. RNaseH_domain. IPR000477. RVT. IPR001878. Znf_CCHC. [Graphical view]
Pfam	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]
SMART	SM00343. ZnF_C2HC. 1 hit. [Graphical view]
SUPFAM	SSF50630. Pept_Aspartic. 1 hit. SSF47943. Retrov_capsid_N. 1 hit. SSF47836. Retrovir_matrix. 1 hit. SSF53098. RNaseH_fold. 2 hits. SSF57756. SSF57756. 1 hit.
PROSITE	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]
ProtoNet	Search...

Entry information

Entry name

POL_XMRV4

Accession

Primary (citable) accession number: Q2F7J0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 19, 2010
Last sequence update:	March 21, 2006
Last modified:	April 3, 2013
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program