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Protein

Gag-Pro-Pol polyprotein

Gene

gag-pro-pol

Organism
Human T-cell leukemia virus 1 (isolate Caribbea HS-35 subtype A) (HTLV-1)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Matrix protein p19 targets Gag, Gag-Pro and Gag-Pro-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).By similarity
Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex.By similarity
Nucleocapsid protein p15 is involved in the packaging and encapsidation of two copies of the genome.By similarity
The aspartyl protease mediates proteolytic cleavages of Gag, Gag-Pro and Gag-Pro-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 (By similarity). Displays maximal activity during the budding process just prior to particle release from the cell. Hydrolyzes host EIF4GI in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response.By similarity1 Publication
Reverse transcriptase (RT) is a multifunctional enzyme that converts the viral 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-Pro 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 primer. 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).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 dinucleotides OH's at the 3' ends. In the second step, the PIC access cell chromosomes during cell division. 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 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands (see above) are filled in and then ligated (By similarity).By similarity

Miscellaneous

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 switching 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).By similarity
HTLV-1 lineages are divided in four clades, A (Cosmopolitan), B (Central African group), C (Melanesian group) and D (New Central African group).

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:
  • Mg2+By similarityNote: Binds 2 magnesium ions for reverse transcriptase polymerase activity.By similarity
  • Mg2+By similarityNote: Binds 2 magnesium ions for ribonuclease H (RNase H) activity.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei481For protease activity; shared with dimeric partnerPROSITE-ProRule annotation1
Metal bindingi680Magnesium; catalytic; for reverse transcriptase activityBy similarity1
Metal bindingi755Magnesium; catalytic; for reverse transcriptase activityBy similarity1
Metal bindingi756Magnesium; catalytic; for reverse transcriptase activityBy similarity1
Metal bindingi1040Magnesium; catalytic; for RNase H activityBy similarity1
Metal bindingi1074Magnesium; catalytic; for RNase H activityBy similarity1
Metal bindingi1096Magnesium; catalytic; for RNase H activityBy similarity1
Metal bindingi1157Magnesium; catalytic; for RNase H activityBy similarity1
Metal bindingi1230Magnesium; catalytic; for integrase activityBy similarity1
Metal bindingi1287Magnesium; catalytic; for integrase activityBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri355 – 372CCHC-type 1PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri378 – 395CCHC-type 2PROSITE-ProRule annotationAdd BLAST18
DNA bindingi1393 – 1443Integrase-typePROSITE-ProRule annotationAdd BLAST51

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Gag-Pro-Pol polyprotein
Alternative name(s):
Pr160Gag-Pro-Pol
Cleaved into the following 7 chains:
Matrix protein p19
Short name:
MA
Capsid protein p24
Short name:
CA
Nucleocapsid protein p15-pro
Short name:
NC'
Short name:
NC-pro
Protease (EC:3.4.23.-)
Short name:
PR
Integrase (EC:2.7.7.-By similarity, EC:3.1.-.-By similarity)
Short name:
IN
Gene namesi
Name:gag-pro-pol
OrganismiHuman T-cell leukemia virus 1 (isolate Caribbea HS-35 subtype A) (HTLV-1)
Taxonomic identifieri11927 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeDeltaretrovirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000110593 Componenti: Genome
  • UP000001061 Componenti: Genome

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Capsid protein, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved; by hostBy similarity
ChainiPRO_00002599402 – 1462Gag-Pro-Pol polyproteinAdd BLAST1461
ChainiPRO_00002599412 – 130Matrix protein p19By similarityAdd BLAST129
ChainiPRO_0000259942131 – 344Capsid protein p24By similarityAdd BLAST214
ChainiPRO_0000259943345 – 449Nucleocapsid protein p15-proBy similarityAdd BLAST105
ChainiPRO_0000259944450 – 574ProteaseBy similarityAdd BLAST125
PeptideiPRO_0000259945575 – 582p1By similarity8
ChainiPRO_0000038875583 – 1167Reverse transcriptase/ribonuclease HBy similarityAdd BLAST585
ChainiPRO_00000388761168 – 1462IntegraseBy similarityAdd BLAST295

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine; by hostBy similarity1
Modified residuei105Phosphoserine; by host MAPK1By similarity1

Post-translational modificationi

Specific enzymatic cleavages by the viral protease yield mature proteins. The polyprotein is cleaved during and after budding, this process is termed maturation. The protease is autoproteolytically processed at its N- and C-termini (By similarity).By similarity
Phosphorylation of the matrix protein p19 by MAPK1 seems to play a role in budding.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei130 – 131Cleavage; by viral proteaseBy similarity2
Sitei344 – 345Cleavage; by viral proteaseBy similarity2
Sitei449 – 450Cleavage; by viral proteaseBy similarity2
Sitei574 – 575Cleavage; by viral proteaseBy similarity2
Sitei582 – 583Cleavage; by viral proteaseBy similarity2
Sitei1167 – 1168Cleavage; by viral proteaseBy similarity2

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Interactioni

Subunit structurei

Interacts with human TSG101 and NEDD4. These interactions are essential for budding and release of viral particles (By similarity).By similarity

Protein-protein interaction databases

ELMiP14078.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ZNYX-ray2.40B121-130[»]
ProteinModelPortaliP14078.
SMRiP14078.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini476 – 554Peptidase A2PROSITE-ProRule annotationAdd BLAST79
Domaini614 – 804Reverse transcriptasePROSITE-ProRule annotationAdd BLAST191
Domaini1031 – 1165RNase HPROSITE-ProRule annotationAdd BLAST135
Domaini1219 – 1388Integrase catalyticPROSITE-ProRule annotationAdd BLAST170

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi118 – 121PPXY motif4
Motifi124 – 127PTAP/PSAP motif4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi95 – 144Pro-richAdd BLAST50
Compositional biasi657 – 660Poly-Ser4

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. Matrix protein p19 contains two L domains: a PTAP/PSAP motif which interacts with the UEV domain of TSG101, and a PPXY motif which binds to the WW domains of HECT (homologous to E6-AP C-terminus) E3 ubiquitin ligases, like NEDD4 (By similarity).By similarity
The capsid protein N-terminus seems to be involved in Gag-Gag interactions.By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri355 – 372CCHC-type 1PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri378 – 395CCHC-type 2PROSITE-ProRule annotationAdd BLAST18

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

OrthoDBiVOG09000057.

Family and domain databases

Gene3Di1.10.1200.30. 1 hit.
1.10.185.10. 1 hit.
1.10.375.10. 1 hit.
2.40.70.10. 1 hit.
3.30.420.10. 2 hits.
4.10.60.10. 3 hits.
InterProiView protein in InterPro
IPR001969. Aspartic_peptidase_AS.
IPR003139. D_retro_matrix.
IPR000721. Gag_p24.
IPR001037. Integrase_C_retrovir.
IPR001584. Integrase_cat-core.
IPR003308. Integrase_Zn-bd_dom_N.
IPR001995. Peptidase_A2_cat.
IPR021109. Peptidase_aspartic_dom.
IPR018061. Retropepsins.
IPR008916. Retrov_capsid_C.
IPR008919. Retrov_capsid_N.
IPR010999. Retrovr_matrix.
IPR012337. RNaseH-like_dom.
IPR002156. RNaseH_domain.
IPR000477. RT_dom.
IPR001878. Znf_CCHC.
PfamiView protein in Pfam
PF02228. Gag_p19. 1 hit.
PF00607. Gag_p24. 1 hit.
PF00552. IN_DBD_C. 1 hit.
PF02022. Integrase_Zn. 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.
SMARTiView protein in SMART
SM00343. ZnF_C2HC. 2 hits.
SUPFAMiSSF47353. SSF47353. 1 hit.
SSF47836. SSF47836. 1 hit.
SSF47943. SSF47943. 1 hit.
SSF50122. SSF50122. 1 hit.
SSF50630. SSF50630. 1 hit.
SSF53098. SSF53098. 1 hit.
SSF57756. SSF57756. 1 hit.
PROSITEiView protein in PROSITE
PS50175. ASP_PROT_RETROV. 1 hit.
PS00141. ASP_PROTEASE. 1 hit.
PS50994. INTEGRASE. 1 hit.
PS51027. INTEGRASE_DBD. 1 hit.
PS50879. RNASE_H. 1 hit.
PS50878. RT_POL. 1 hit.
PS50158. ZF_CCHC. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by ribosomal frameshifting. AlignAdd to basket

Note: This strategy of translation probably allows the virus to modulate the quantity of each viral protein.
Isoform Gag-Pol polyprotein (identifier: P14078-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGQIFSRSAS PIPRPPRGLA AHHWLNFLQA AYRLEPGPSS YDFHQLKKFL
60 70 80 90 100
KIALETPVWI CPINYSLLAS LLPKGYPGRV NEILHILIQT QAQIPSRPAP
110 120 130 140 150
PPPSSSTHDP PDSDPQIPPP YVEPTAPQVL PVMHPHGAPP NHRPWQMKDL
160 170 180 190 200
QAIKQEVSQA APGSPQFMQT IRLAVQQFDP TAKDLQDLLQ YLCSSLVASL
210 220 230 240 250
HHQQLDSLIS EAETRGITGY NPLAGPLRVQ ANNPQQQGLR REYQQLWLAA
260 270 280 290 300
FAALPGSAKD PSWASILQGL EEPYHAFVER LNIALDNGLP EGTPKDPILR
310 320 330 340 350
SLAYSNANKE CQKLLQARGH TNSPLGDMLR ACQAWTPKDK TKVLVVQPKK
360 370 380 390 400
PPPNQPCFRC GKAGHWSRDC TQPRPPPGPC PLCQDPTHWK RDCPRLKPTI
410 420 430 440 450
PEPEPEEDAL LLDLPADIPH PKNLHRGGGL TSPPTLQQVL PNQDPTSILP
460 470 480 490 500
VIPLDPARRP VIKAQIDTQT SHPKTIEALL DTGADMTVLP IALFSSNTPL
510 520 530 540 550
KNTSVLGAGG QTQDHFKLTS LPVLIRLPFR TTPIVLTSCL VDTKNNWAII
560 570 580 590 600
GRDALQQCQG VLYLPEAKRP PVILPIQAPA VLGLEHLPRP PEISQFPLNP
610 620 630 640 650
ERLQALQHLV RKALEAGHIE PYTGPGNNPV FPVKKANGTW RFIHDLRATN
660 670 680 690 700
SLTIDLSSSS PGPPDLSSLP TTLAHLQTID LKDAFFQIPL PKQFQPYFAF
710 720 730 740 750
TVPQQCNYGP GTRYAWRVLP QGFKNSPTLF EMQLAHILQP IRQAFPQCTI
760 770 780 790 800
LQYMDDILLA SPSHADLQLL SEATMASLIS HGLPVSENKT QQTPGTIKFL
810 820 830 840 850
GQIISPNHLT YDAVPKVPIR SRWALPELQA LLGEIQWVSK GTPTLRQPLH
860 870 880 890 900
SLYCALQRHT DPRDQIYLNP SQVQSLVQLR QALSQNCRSR LVQTLPLLGA
910 920 930 940 950
IMLTLTGTTT VVFQSKQQWP LVWLHAPLPH TSQCPWGQLL ASAVLLLDKY
960 970 980 990 1000
TLQSYGLLCQ TIHHNISTQT FNQFIQTSDH PSVPILLHHS HRFKNLGAQT
1010 1020 1030 1040 1050
GELWNTFLKT TAPLAPVKAL MPVFTLSPVI INTAPCLFSD GSTSQAAYIL
1060 1070 1080 1090 1100
WDKHILSQRS FPLPPPHKSA QRAELLGLLH GLSSARSWRC LNIFLDSKYL
1110 1120 1130 1140 1150
YHYLRTLALG TFQGRSSQAP FQALLPRLLS RKVVYLHHVR SHTNLPDPIS
1160 1170 1180 1190 1200
RLNALTDALL ITPVLQLSPA DLHSFTHCGQ TALTLQGATT TEASNILRSC
1210 1220 1230 1240 1250
HACRKNNPQH QMPQGHIRRG LLPNHIWQGD ITHFKYKNTL YRLHVWVDTF
1260 1270 1280 1290 1300
SGAISATQKR KETSSEAISS LLQAIAYLGK PSYINTDNGP AYISQDFLNM
1310 1320 1330 1340 1350
CTSLAIRHTT HVPYNPTSSG LVERSNGILK TLLYKYFTDK PDLPMDNALS
1360 1370 1380 1390 1400
IALWTINHLN VLTNCHKTRW QLHHSPRLQP IPETHSLSNK QTHWYYFKLP
1410 1420 1430 1440 1450
GLNSRQWKGP QEALQEAAGA ALIPVSASSA QWIPWRLLKR AACPRPVGGP
1460
ADPKEKDHQH HG
Note: Produced by -1 ribosomal frameshifting at the gag-pol genes boundary.
Length:1,462
Mass (Da):162,686
Last modified:January 23, 2007 - v3
Checksum:i89F03B47B8BA7805
GO
Isoform Gag-Pro polyprotein (identifier: P14074-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P14074.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by -1 ribosomal frameshifting at the gag-pro genes boundary.
Length:651
Mass (Da):71,664
GO
Isoform Gag polyprotein (identifier: P14076-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P14076.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by conventional translation.
Length:429
Mass (Da):47,514
GO

Sequence cautioni

The sequence BAA02931 differs from that shown. Reason: Erroneous gene model prediction.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13784 Genomic DNA. Translation: BAA02931.1. Sequence problems.
AF033817 Genomic DNA. Translation: AAC82581.1.
PIRiC28136. GNLJCN.
RefSeqiNP_057860.1. NC_001436.1.

Genome annotation databases

GeneIDi1724740.
KEGGivg:1724740.

Keywords - Coding sequence diversityi

Ribosomal frameshifting

Similar proteinsi

Entry informationi

Entry nameiPOL_HTL1C
AccessioniPrimary (citable) accession number: P14078
Secondary accession number(s): O56228
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 23, 2007
Last modified: September 27, 2017
This is version 139 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references