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Protein

Gag-Pol polyprotein

Gene

pro-pol

Organism
Koala retrovirus (KoRV)
Status
Reviewed-Annotation score: -Protein inferred from homologyi

Functioni

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-Pol, or to Gag-Pol binding host factors. Interaction with HECT ubiquitin ligases probably links the viral protein to the host ESCRT pathway and facilitates release.By similarity
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 pre-integration complex.By similarity
RNA-binding phosphoprotein p12: Constituent of the pre-integration complex (PIC) which tethers the latter to mitotic chromosomes. This allows the integration of the viral genome into the host DNA.By similarity
Capsid protein p30: Forms the spherical core of the virion that encapsulates the genomic RNA-nucleocapsid complex.By similarity
Nucleocapsid protein p10-Pol: Involved in the packaging and encapsidation of two copies of the genome (By similarity). Binds with high affinity to conserved UCUG elements within the packaging signal, located near the 5'-end of the genome (By similarity). This binding is dependent on genome dimerization (By similarity). Acts as a nucleic acid chaperone which is involved in rearrangement of nucleic acid secondary structures during gRNA retrotranscription (By similarity).By similarity
Protease: 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.PROSITE-ProRule annotation
Reverse transcriptase/ribonuclease H: RT 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.Sequence analysis
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

Miscellaneous

Gag-Pol polyprotein: 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 521-Asp and 523-Gly.By similarity
Nucleocapsid protein p10-Pol: Nucleocapsid protein p10-Pol 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
Reverse transcriptase/ribonuclease H: 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.PROSITE-ProRule annotation

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:
  • Mg2+PROSITE-ProRule annotationNote: The RT polymerase active site binds 2 magnesium ions.PROSITE-ProRule annotation
  • Mg2+By similarityNote: Binds 1 magnesium ions for ribonuclease H (RNase H) activity.By similarity
  • Mg2+By similarityNote: Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions.By similarity

Enzyme regulationi

Protease: Most efficiently inhibited by Amprenavir, which is able to block Gag-Pol processing in infected cells.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei549Protease; shared with dimeric partnerPROSITE-ProRule annotation1
Metal bindingi789Magnesium; catalytic; for reverse transcriptase activityPROSITE-ProRule annotation1
Metal bindingi863Magnesium; catalytic; for reverse transcriptase activityPROSITE-ProRule annotation1
Metal bindingi864Magnesium; catalytic; for reverse transcriptase activityPROSITE-ProRule annotation1
Metal bindingi1162Magnesium; catalytic; for RNase H activityPROSITE-ProRule annotation1
Metal bindingi1200Magnesium; catalytic; for RNase H activityPROSITE-ProRule annotation1
Metal bindingi1221Magnesium; catalytic; for RNase H activityPROSITE-ProRule annotation1
Metal bindingi1291MagnesiumPROSITE-ProRule annotation1
Metal bindingi1405Magnesium; catalytic; for integrase activityPROSITE-ProRule annotation1
Metal bindingi1464Magnesium; catalytic; for integrase activityPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri490 – 507CCHC-typePROSITE-ProRule annotationAdd BLAST18
Zinc fingeri1339 – 1377HHCC-typeBy similarityAdd BLAST39

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAspartyl protease, DNA-binding, DNA-directed DNA polymerase, Endonuclease, Hydrolase, Multifunctional enzyme, Nuclease, Nucleotidyltransferase, Protease, RNA-binding, RNA-directed DNA polymerase, Transferase, Viral nucleoprotein
Biological processDNA integration, DNA recombination, Host-virus interaction, Viral genome integration, Virus entry into host cell
LigandMagnesium, Metal-binding, Zinc

Protein family/group databases

MEROPSiA02.020

Names & Taxonomyi

Protein namesi
Recommended name:
Gag-Pol polyprotein
Alternative name(s):
Pr125Pol
Cleaved into the following 6 chains:
Matrix protein p15
Short name:
MA
Alternative name(s):
pp12
Capsid protein p30
Short name:
CA
Alternative name(s):
p87
Integrase (EC:2.7.7.-By similarity, EC:3.1.-.-By similarity)
Short name:
IN
Alternative name(s):
p42
Gene namesi
Name:pro-pol
OrganismiKoala retrovirus (KoRV)
Taxonomic identifieri394239 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeGammaretrovirus
Virus hostiPhascolarctos cinereus (Koala) [TaxID: 38626]
Proteomesi
  • UP000101411 Componenti: Genome
  • UP000007765 Componenti: Genome

Subcellular locationi

Gag-Pol polyprotein :
  • Virion By similarity
  • Host cell membrane By similarity; Lipid-anchor By similarity
  • Host late endosome membrane By similarity; Lipid-anchor By similarity
  • host multivesicular body By similarity
  • Note: These locations are probably linked to virus assembly sites.By similarity
Matrix protein p15 :
  • Virion By similarity
Capsid protein p30 :
  • Virion By similarity
Nucleocapsid protein p10-Pol :
  • Virion By similarity
RNA-binding phosphoprotein p12 :
  • Host cytoplasm By similarity
  • Note: Localizes to the host cytoplasm early in infection and binds to the mitotic chromosomes later on.By similarity

GO - Cellular componenti

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedSequence analysis
ChainiPRO_00002494312 – 1687Gag-Pol polyproteinAdd BLAST1686
ChainiPRO_00004428562 – 128Matrix protein p15Add BLAST127
ChainiPRO_0000442857129 – 196RNA-binding phosphoprotein p12Add BLAST68
ChainiPRO_0000442858197 – 455Capsid protein p30Add BLAST259
ChainiPRO_0000442859456 – 517Nucleocapsid protein p10-PolAdd BLAST62
ChainiPRO_0000249432?518 – 1310Protease/Reverse transcriptase/ribonuclease HBy similarityAdd BLAST793
ChainiPRO_00002494331311 – 1687IntegraseAdd BLAST377

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine; by hostSequence analysis1

Post-translational modificationi

Gag-Pol polyprotein: 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
RNA-binding phosphoprotein p12: Phosphorylated on serine residues.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei128 – 129Cleavage; by viral proteaseBy similarity2
Sitei196 – 197Cleavage; by viral proteaseBy similarity2
Sitei455 – 456Cleavage; by viral proteaseBy similarity2
Sitei517 – 518Cleavage; by viral proteaseBy similarity2
Sitei1310 – 1311Cleavage; by viral proteaseBy similarity2

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PRIDEiQ9TTC1

Interactioni

Subunit structurei

Capsid protein p30: Homohexamer; further associates as homomultimer (By similarity). Capsid protein p30: The virus core is composed of a lattice formed from hexagonal rings, each containing six capsid monomers (By similarity). Gag-Pol polyprotein: Interacts (via PPXY motif) with host NEDD4 (By similarity). Gag-Pol polyprotein: Interacts (via PSAP motif) with host TSG101 (By similarity). Reverse transcriptase/ribonuclease H: The reverse transcriptase is a monomer (Potential). Reverse transcriptase/ribonuclease H: Interacts (via RNase domains) with host release factor ETF1; this interaction is essential for translational readthrough of amber codon between viral gag and pol genes, as well as for viral replication (By similarity). Integrase: Homodimer (By similarity).PROSITE-ProRule annotationBy similarity

Structurei

3D structure databases

ProteinModelPortaliQ9TTC1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini544 – 614Peptidase A2PROSITE-ProRule annotationAdd BLAST71
Domaini721 – 912Reverse transcriptasePROSITE-ProRule annotationAdd BLAST192
Domaini1153 – 1299RNase HPROSITE-ProRule annotationAdd BLAST147
Domaini1394 – 1552Integrase catalyticPROSITE-ProRule annotationAdd BLAST159

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili408 – 453Sequence analysisAdd BLAST46

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi108 – 111PTAP/PSAP motifBy similarity4
Motifi140 – 143PPXY motifBy similarity4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi92 – 217Pro-richPROSITE-ProRule annotationAdd BLAST126
Compositional biasi1677 – 1682Poly-ArgSequence analysis6

Domaini

Gag polyprotein: Late-budding domains (L domains) are short sequence motifs essential for viral particle budding. They recruit proteins of the host ESCRT machinery (Endosomal Sorting Complex Required for Transport) or ESCRT-associated proteins. RNA-binding phosphoprotein p12 contains one L domain: a PPXY motif which potentially interacts with the WW domain 3 of NEDD4 E3 ubiquitin ligase. Matrix protein p15 contains one L domain: a PTAP/PSAP motif, which potentially interacts with the UEV domain of TSG101.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).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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri490 – 507CCHC-typePROSITE-ProRule annotationAdd BLAST18
Zinc fingeri1339 – 1377HHCC-typeBy similarityAdd BLAST39

Keywords - Domaini

Coiled coil, Zinc-finger

Family and domain databases

CDDicd06095 RP_RTVL_H_like, 1 hit
Gene3Di1.10.150.180, 1 hit
1.10.375.10, 1 hit
2.40.70.10, 1 hit
3.30.420.10, 2 hits
InterProiView protein in InterPro
IPR001969 Aspartic_peptidase_AS
IPR000840 G_retro_matrix
IPR036946 G_retro_matrix_sf
IPR003036 Gag_P30
IPR001584 Integrase_cat-core
IPR001995 Peptidase_A2_cat
IPR021109 Peptidase_aspartic_dom_sf
IPR018061 Retropepsins
IPR008919 Retrov_capsid_N
IPR010999 Retrovr_matrix
IPR012337 RNaseH-like_sf
IPR002156 RNaseH_domain
IPR036397 RNaseH_sf
IPR034145 RP_RTVL-H-like
IPR000477 RT_dom
IPR001878 Znf_CCHC
IPR036875 Znf_CCHC_sf
IPR015416 Znf_H2C2_histone_UAS-bd
PfamiView protein in Pfam
PF01140 Gag_MA, 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
PF00098 zf-CCHC, 1 hit
PF09337 zf-H2C2, 1 hit
SMARTiView protein in SMART
SM00343 ZnF_C2HC, 1 hit
SUPFAMiSSF47836 SSF47836, 1 hit
SSF47943 SSF47943, 1 hit
SSF50630 SSF50630, 1 hit
SSF53098 SSF53098, 2 hits
SSF57756 SSF57756, 1 hit
PROSITEiView protein in 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

Sequencei

Sequence statusi: Complete.

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

Q9TTC1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGQGESTPLS LTLDHWKDVK TRAHNLSVEI RKGKWQTFCS SEWPTFEVGW
60 70 80 90 100
PPEGTFNPSI ISAVKRIVFQ ETGGHPDQVP YIIVWQDLSN SPPPWVPPLA
110 120 130 140 150
KIAVASGQDN GRKSAGGRPS APSRLPIYPE TDSLFLLSEP PPYPTSPPPP
160 170 180 190 200
PAPHAARPAP GLMAEGLGSE GPAAGTRSRR PRSPTGDTGP DSTVALPLRA
210 220 230 240 250
VGPPAEPNGL VPLQYWPFSS ADLYNWKSNH PSFSENPTGL TGLLESLMFS
260 270 280 290 300
HQPTWDDCQQ LLQVLFTTEE RERILLEARK NVLGVNGAPT QLENLINEAF
310 320 330 340 350
PLNRPQWDHN TAEGRERLLV YRRTLVAGLK GAARRPTNLA KVREVLQGPT
360 370 380 390 400
EPPSVFLERL MEAYRRYTPF DPSSEGQKAA VAMSFIGQSA PDIKKKLQRL
410 420 430 440 450
EGLQDHSLQD LIKEAEKVYH KRETEEEKQE REKKETEERE RRRDRRQEKN
460 470 480 490 500
LTKILAAVVS EKGFRGRQAG NLSNRAMRAP REGRPPLDKD QCAYCKERGH
510 520 530 540 550
WARECPRKKN ARETNVLTLG DQGSRGSDPL PEPRVTLTVE GIPTEFLVDT
560 570 580 590 600
GAEHSVLTKP MGKMGSKRTV VAGATGSKVY PWTTKRLLKI GQKQVTHSFL
610 620 630 640 650
VIPECPAPLL GRDLLTKLKA QIQFSTEGPQ VTWEDRPAMC LVLNLEEEYR
660 670 680 690 700
LHEKPVPPSI DPSWLQLFPM VWAEKAGMGL ANQVPPVVVE LKSDASPVAV
710 720 730 740 750
RQYPMSKEAR EGIRPHIQRF LDLGILVPCQ SPWNTPLLPV KKPGTNDYRP
760 770 780 790 800
VQDLREVNKR VQDIHPTVPN PYNLLSSLPP SHTWYSVLDL KDAFFCLKLH
810 820 830 840 850
PNSQPLFAFE WRDPEKGNTG QLTWTRLPQG FKNSPTLFDE ALHRDLASFR
860 870 880 890 900
ALNPQVVMLQ YVDDLLVAAP TYRDCKEGTR RLLQELSKLG YRVSAKKAQL
910 920 930 940 950
CREEVTYLGY LLKGGKRWLT PARKATVMKI PTPTTPRQVR EFLGTAGFCR
960 970 980 990 1000
LWIPGFASLA APLYPLTREK VPFTWTEAHQ EAFGRIKEAL LSAPALALPD
1010 1020 1030 1040 1050
LTKPFALYVD EKEGVARGVL TQTLGPWRRP VAYLSKKLDP VASGWPTCLK
1060 1070 1080 1090 1100
AIAAVALLLK DADKLTLGQN VLVIAPHNLE SIVRQPPDRW MTNARMTHYQ
1110 1120 1130 1140 1150
SLLLNERVSF APPAILNPAT LLPVESDDTP IHICSEILAE ETGTRPDLRD
1160 1170 1180 1190 1200
QPLPGVPAWY TDGSSFIMDG RRQAGAAIVD NKRTVWASNL PEGTSAQKAE
1210 1220 1230 1240 1250
LIALTQALRL AEGKSINIYT DSRYAFATAH VHGAIYKQRG LLTSAGKDIK
1260 1270 1280 1290 1300
NKEEILALLE AIHLPKRVAI IHCPGHQRGT DPVATGNRKA DEAAKQAAQS
1310 1320 1330 1340 1350
TRILTETTKN QEHFEPTRGK IKPRELTPDQ GREFIQRLHQ LTHLGPDKLL
1360 1370 1380 1390 1400
QLVGRTSFHI PNLQSVVREI TSKCQVCAVT NAVTTYREPG RRQRGDRPGV
1410 1420 1430 1440 1450
YWEVDFTEVK PGRYGNRYLL VFIDTFSGWV EAFPTKTETA LTVCKKILEE
1460 1470 1480 1490 1500
ILPRFGIPKV LGSDNGPAFV AQVSQGLATQ LGIDWKLHCA YRPQSSGQVE
1510 1520 1530 1540 1550
RMNRTIKETL TKLALETGGK DWVTLLPLAL LRARNTPGQF GLTPYEILHG
1560 1570 1580 1590 1600
GPPPVLASGE VVGSNGDFFP VLFTHLKALE VVRTQIWDQI KEAYRPGTVA
1610 1620 1630 1640 1650
IPHPFQVGDR VLVRRHRSGS LEPRWKGPYL VLLTTPTAVK VDGIAAWVHA
1660 1670 1680
SHLKPAPPGA PDESWELEKT DHPLKLRVRR RRNESTA
Length:1,687
Mass (Da):188,187
Last modified:January 31, 2018 - v2
Checksum:i22A95F1D05BCB5AA
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti47E → K1 Publication1
Natural varianti464F → S1 Publication1
Natural varianti566S → P1 Publication1
Natural varianti1382A → T1 Publication1
Natural varianti1389P → S1 Publication1
Natural varianti1484D → N1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF151794 Genomic DNA Translation: AAF15098.1
AB721500 Genomic DNA Translation: BAM67146.1

Keywords - Coding sequence diversityi

RNA suppression of termination

Similar proteinsi

Entry informationi

Entry nameiPOL_KORV
AccessioniPrimary (citable) accession number: Q9TTC1
Secondary accession number(s): K7ZK66
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: January 31, 2018
Last modified: March 28, 2018
This is version 94 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome
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Main funding by: National Institutes of Health