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Protein

Gag-Pol polyprotein

Gene

pol

Organism
Gibbon ape leukemia virus (GALV)
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 520-Asp and 522-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 sitei548Protease; shared with dimeric partnerPROSITE-ProRule annotation1
Metal bindingi788Magnesium; catalyticPROSITE-ProRule annotation1
Metal bindingi862Magnesium; catalyticPROSITE-ProRule annotation1
Metal bindingi863Magnesium; catalyticPROSITE-ProRule annotation1
Metal bindingi1161MagnesiumPROSITE-ProRule annotation1
Metal bindingi1199MagnesiumPROSITE-ProRule annotation1
Metal bindingi1220MagnesiumPROSITE-ProRule annotation1
Metal bindingi1290MagnesiumPROSITE-ProRule annotation1
Metal bindingi1404Magnesium; catalyticPROSITE-ProRule annotation1
Metal bindingi1463Magnesium; catalyticPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri489 – 506CCHC-typePROSITE-ProRule annotationAdd BLAST18
Zinc fingeri1338 – 1376HHCC-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

Names & Taxonomyi

Protein namesi
Recommended name:
Gag-Pol polyprotein
Cleaved into the following 7 chains:
Matrix protein p15
Short name:
MA
Alternative name(s):
pp12
Capsid protein p30
Short name:
CA
Protease (EC:3.4.23.-PROSITE-ProRule annotation)
Reverse transcriptase/ribonuclease H (EC:2.7.7.49PROSITE-ProRule annotation, EC:2.7.7.7PROSITE-ProRule annotation, EC:3.1.26.4PROSITE-ProRule annotation)
Short name:
RT
Integrase (EC:2.7.7.-By similarity, EC:3.1.-.-By similarity)
Short name:
IN
Gene namesi
Name:pol
OrganismiGibbon ape leukemia virus (GALV)
Taxonomic identifieri11840 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeGammaretrovirus
Virus hostiHylobatidae (gibbons) [TaxID: 9577]
Proteomesi

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
Protease :
  • 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_00002597192 – 1686Gag-Pol polyproteinAdd BLAST1685
ChainiPRO_00004428832 – 125Matrix protein p15Add BLAST124
ChainiPRO_0000442884126 – 195RNA-binding phosphoprotein p12Add BLAST70
ChainiPRO_0000442885196 – 454Capsid protein p30Add BLAST259
ChainiPRO_0000442886455 – 516Nucleocapsid protein p10-PolAdd BLAST62
ChainiPRO_0000026128517 – 640ProteaseAdd BLAST124
ChainiPRO_0000259720641 – 1309Reverse transcriptase/ribonuclease HAdd BLAST669
ChainiPRO_00002597211310 – 1686IntegraseAdd 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
Sitei125 – 126Cleavage; by viral proteaseBy similarity2
Sitei195 – 196Cleavage; by viral proteaseBy similarity2
Sitei454 – 455Cleavage; by viral proteaseBy similarity2
Sitei516 – 517Cleavage; by viral proteaseBy similarity2
Sitei640 – 641Cleavage; by viral proteaseBy similarity2
Sitei1309 – 1310Cleavage; by viral proteaseBy similarity2

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PRIDEiP21414

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

ProteinModelPortaliP21414
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini543 – 613Peptidase A2PROSITE-ProRule annotationAdd BLAST71
Domaini720 – 911Reverse transcriptasePROSITE-ProRule annotationAdd BLAST192
Domaini1152 – 1298RNase HPROSITE-ProRule annotationAdd BLAST147
Domaini1393 – 1551Integrase catalyticPROSITE-ProRule annotationAdd BLAST159

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili407 – 444Sequence analysisAdd BLAST38

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi116 – 119PTAP/PSAP motifBy similarity4
Motifi139 – 142PPXY motifBy similarity4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi92 – 216Pro-richPROSITE-ProRule annotationAdd BLAST125
Compositional biasi131 – 134Poly-LeuSequence analysis4
Compositional biasi1676 – 1681Poly-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

Sequence similaritiesi

Belongs to the retroviral Pol polyprotein family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri489 – 506CCHC-typePROSITE-ProRule annotationAdd BLAST18
Zinc fingeri1338 – 1376HHCC-typeBy similarityAdd BLAST39

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

OrthoDBiVOG0900018N

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.

P21414-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGQDNSTPIS LTLNHWRDVR TRAHNLSVEI KKGKWQTFCS SEWPTFGVGW
60 70 80 90 100
PPEGTFNLSV IFAVKKIVFQ ENGGHPDQVP YIVVWQDLAQ NPPPWVPASA
110 120 130 140 150
KVAVVSDTRR PVAGRPSAPP RPPIYPATDD LLLLSEPTPP PYPAALPPPL
160 170 180 190 200
APQAIGPPSG QMPDSSDPEG PAAGTRSRRA RSPADNSGPD STVILPLRAI
210 220 230 240 250
GPPAEPNGLV PLQYWPFSSA DLYNWKSNHP SFSENPAGLT GLLESLMFSH
260 270 280 290 300
QPTWDDCQQL LQILFTTEER ERILLEARKN VLGDNGAPTQ LENLINEAFP
310 320 330 340 350
LNRPHWDYNT AAGRERLLVY RRTLVAGLKG AARRPTNLAK VREVLQGPAE
360 370 380 390 400
PPSVFLERLM EAYRRYTPFD PSSEGQQAAV AMAFIGQSAP DIKKKLQRLE
410 420 430 440 450
GLQDYSLQDL VKEAEKVYHK RETEEERQER EKKEAEEKER RRDRPKKKNL
460 470 480 490 500
TKILAAVVSR EGSTGRQTGN LSNQAKKTPR DGRPPLDKDQ CAYCKEKGHW
510 520 530 540 550
ARECPRKKHV REAKVLALDN XGSQGSDPLP EPRVTLTVEG TPIEFLVDTG
560 570 580 590 600
AEHSVLTQPM GKVGSRRTVV EGATGSKVYP WTTKRLLKIG HKQVTHSFLV
610 620 630 640 650
IPECPAPLLG RDLLTKLKAQ IQFSAEGPQV TWGERPTMCL VLNLEEEYRL
660 670 680 690 700
HEKPVPSSID PSWLQLFPTV WAERAGMGLA NQVPPVVVEL RSGASPVAVR
710 720 730 740 750
QYPMSKEARE GIRPHIQKFL DLGVLVPCRS PWNTPLLPVK KPGTNDYRPV
760 770 780 790 800
QDLREINKRV QDIHPTVPNP YNLLSSLPPS YTWYSVLDLK DAFFCLRLHP
810 820 830 840 850
NSQPLFAFEW KDPEKGNTGQ LTWTRLPQGF KNSPTLFDEA LHRDLAPFRA
860 870 880 890 900
LNPQVVLLQY VDDLLVAAPT YEDCKKGTQK LLQELSKLGY RVSAKKAQLC
910 920 930 940 950
QREVTYLGYL LKEGKRWLTP ARKATVMKIP VPTTPRQVRE FLGTAGFCRL
960 970 980 990 1000
WIPGFASLAA PLYPLTKESI PFIWTEEHQQ AFDHIKKALL SAPALALPDL
1010 1020 1030 1040 1050
TKPFTLYIDE RAGVARGVLT QTLGPWRRPV AYLSKKLDPV ASGWPTCLKA
1060 1070 1080 1090 1100
VAAVALLLKD ADKLTLGQNV TVIASHSLES IVRQPPDRWM TNARMTHYQS
1110 1120 1130 1140 1150
LLLNERVSFA PPAVLNPATL LPVESEATPV HRCSEILAEE TGTRRDLEDQ
1160 1170 1180 1190 1200
PLPGVPTWYT DGSSFITEGK RRAGAPIVDG KRTVWASSLP EGTSAQKAEL
1210 1220 1230 1240 1250
VALTQALRLA EGKNINIYTD SRYAFATAHI HGAIYKQRGL LTSAGKDIKN
1260 1270 1280 1290 1300
KEEILALLEA IHLPRRVAII HCPGHQRGSN PVATGNRRAD EAAKQAALST
1310 1320 1330 1340 1350
RVLAGTTKPQ EPIEPAQEKT RPRELTPDRG KEFIKRLHQL THLGPEKLLQ
1360 1370 1380 1390 1400
LVNRTSLLIP NLQSAVREVT SQCQACAMTN AVTTYRETGK RQRGDRPGVY
1410 1420 1430 1440 1450
WEVDFTEIKP GRYGNKYLLV FIDTFSGWVE AFPTKTETAL IVCKKILEEI
1460 1470 1480 1490 1500
LPRFGIPKVL GSDNGPAFVA QVSQGLATQL GINWKLHCAY RPQSSGQVER
1510 1520 1530 1540 1550
MNRTIKETLT KLALETGGKD WVTLLPLALL RARNTPGRFG LTPYEILYGG
1560 1570 1580 1590 1600
PPPILESGET LGPDDRFLPV LFTHLKALEI VRTQIWDQIK EVYKPGTVTI
1610 1620 1630 1640 1650
PHPFQVGDQV LVRRHRPSSL EPRWKGPYLV LLTTPTAVKV DGIAAWVHAS
1660 1670 1680
HLKPAPPSAP DESWELEKTD HPLKLRIRRR RDESAK
Length:1,686
Mass (Da):188,090
Last modified:January 31, 2018 - v2
Checksum:i09E371779382C400
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M26927 Genomic RNA Translation: AAA46810.1
PIRiB32595 GNLJGL
RefSeqiNP_056790.1, NC_001885.2

Genome annotation databases

GeneIDi1491893
KEGGivg:1491893

Keywords - Coding sequence diversityi

RNA suppression of termination

Similar proteinsi

Entry informationi

Entry nameiPOL_GALV
AccessioniPrimary (citable) accession number: P21414
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: January 31, 2018
Last modified: May 23, 2018
This is version 121 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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