POL Polyprotein
HIV POL
encodes the viral enzymes protease, reverse transcriptase, and integrase. The enzymes are produced as a GAG-POL precursor polyprotein, which
is processed by viral protease.
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Protease - p15
Reverse Transcriptase - p51
Reverse Transcriptase and RNase H - p66
RNase H - p15
Integrase - p31
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Isoforms:
- POL Polyprotein (99 amino acids)
- p160 - GAG-POL Polyprotein
Cleavage site:
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Localization:
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Function:
- precursor for viral enzymes
- during viral maturation, viral protease cleaves the Pol polyprotein away from Gag, and further digests it to separate it into 4 proteins: protease, reverse transcriptase, RNase H, and Integrase
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Additional
Information:
- All of the pol gene products can be found in the capsid of the virion
- the Gag-Pol precursor is generated by a ribosome frameshift at the C-terminus of GAG (Ref. #4 & #5)
- the ribosome frameshift is triggered by a specific cis-acting RNA motif (Ref. #4 & #5)
- the cis-acting RNA motif consists of a heptanucleotide sequence followed by a short stem-loop in the distal region of the GAG RNA
- without interrupting translation, the ribosome shifts to the pol reading frame ~5% of the time that the cis-acting RNA motif is encountered
- the frequency of ribosomal frameshifting coincides with the 20:1 ratio of Gag to Gag-Pol precursors
- Protease cleavage does not occur efficiently, and 50% of the Reverse Transcriptase protein remain covalently associated to RNase H
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Genomic Location: [TOP]
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Reference
Sequences: HIV-1
(HXB2):
10 20 30 40 50 60 70
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FFREDLAFLQ GKAREFSSEQ TRANSPTRRE LQVWGRDNNS PSEAGADRQG TVSFNFPQVT LWQRPLVTIK
80 90 100 110 120 130 140
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IGGQLKEALL DTGADDTVLE EMSLPGRWKP KMIGGIGGFI KVRQYDQILI EICGHKAIGT VLVGPTPVNI
150 160 170 180 190 200 210
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IGRNLLTQIG CTLNFPISPI ETVPVKLKPG MDGPKVKQWP LTEEKIKALV EICTEMEKEG KISKIGPENP
220 230 240 250 260 270 280
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YNTPVFAIKK KDSTKWRKLV DFRELNKRTQ DFWEVQLGIP HPAGLKKKKS VTVLDVGDAY FSVPLDEDFR
290 300 310 320 330 340 350
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KYTAFTIPSI NNETPGIRYQ YNVLPQGWKG SPAIFQSSMT KILEPFRKQN PDIVIYQYMD DLYVGSDLEI
360 370 380 390 400 410 420
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GQHRTKIEEL RQHLLRWGLT TPDKKHQKEP PFLWMGYELH PDKWTVQPIV LPEKDSWTVN DIQKLVGKLN
430 440 450 460 470 480 490
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WASQIYPGIK VRQLCKLLRG TKALTEVIPL TEEAELELAE NREILKEPVH GVYYDPSKDL IAEIQKQGQG
500 510 520 530 540 550 560
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QWTYQIYQEP FKNLKTGKYA RMRGAHTNDV KQLTEAVQKI TTESIVIWGK TPKFKLPIQK ETWETWWTEY
570 580 590 600 610 620 630
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WQATWIPEWE FVNTPPLVKL WYQLEKEPIV GAETFYVDGA ANRETKLGKA GYVTNRGRQK VVTLTDTTNQ
640 650 660 670 680 690 700
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KTELQAIYLA LQDSGLEVNI VTDSQYALGI IQAQPDQSES ELVNQIIEQL IKKEKVYLAW VPAHKGIGGN
710 720 730 740 750 760 770
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EQVDKLVSAG IRKVLFLDGI DKAQDEHEKY HSNWRAMASD FNLPPVVAKE IVASCDKCQL KGEAMHGQVD
780 790 800 810 820 830 840
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CSPGIWQLDC THLEGKVILV AVHVASGYIE AEVIPAETGQ ETAYFLLKLA GRWPVKTIHT DNGSNFTGAT
850 860 870 880 890 900 910
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VRAACWWAGI KQEFGIPYNP QSQGVVESMN KELKKIIGQV RDQAEHLKTA VQMAVFIHNF KRKGGIGGYS
920 930 940 950 960 970 980
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AGERIVDIIA TDIQTKELQK QITKIQNFRV YYRDSRNPLW KGPAKLLWKG EGAVVIQDNS DIKVVPRRKA
990 1000
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KIIRDYGKQM AGDDCVASRQ DED
[download in fasta format]
Length:
1003 amino acids
Molecular Weight: 113779 Da
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Protein Domains/Folds/Motifs: [TOP]
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p15 - Protease (99 amino acids)
p51 - Reverse Transcriptase (440 amino acids)
p66 - RT and RNase H (560 amino acids)
p15 - RNase H (120 amino acids)
p31 - Integrase (288 amino acids)
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Secondary Structure prediction:
Low Complexity Region - seg:
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N-glycosylation:
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N-myristoylation:
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Amidation:
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Protein kinase C:
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Casein kinase II:
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Tyrosine kinase:
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cAMP / cGMP kinase:
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Cell attachment motif:
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Asp Protease motif:
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Asp Prot Retro motif:
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Cysteine-rich Region:
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Tryptophan-rich Region:
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Zinc-finger CCHC motif:
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Leucine Zipper motif:
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Protein-Protein Interactions: [TOP]
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Primary and Secondary Database Entries: [TOP]
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Identifiers:
PDB/MMDB: Search for HIV-1 & POL
SwissProt: P04585 (HIV-1 HXB2 Pol)
EMBL: K03455; AAB50259.1 [EMBL/GenBank/DDBJ]
PIR: UNKNOWN
HIV: K03455; POL$HXB2
MEROPS: A02.001
InterPro: IPR000477 - RNA-directed DNA polymerase (RT) family /
IPR001037 - Integrase C-terminal family
IPR001584 - Integrase catalytic domain /
IPR001969 - Eukaryotic/viral aspartic protease active site
IPR001995 - Retroviral Aspartic Protease family/
IPR002156 - RNase H domain
IPR003308 - Integrase N-terminal zinc-binding domain /
IPR009007 - Acid Protease domain
Pfam: PF00078 - RVT / PF00665 - RVE / PF00077 - RVP / PF00075 - RNase H / PF00552 - Integrase
PF02022 - Integrase Zinc-binding
Prints: none
ProDom: PD186096 (residues 13 - 72) / PD000261 (residues 156 - 217) / PD580497 (residues 184 - 227) /
PD492067 (residues 218 - 260) / PD404869 (residues 218 - 285) / PD000379 (residues 261 - 303) /
PD513590 (residues 276 - 316) / PD474846 (residues 294 - 389) / PD000698 (residues 390 - 451) /
PD495523 (residues 462 - 593) / PD390352 (residues 589 - 705) / PD000727 (residues 594 - 661) /
PD416714 (residues 664 - 704) / PD582846 (residues 675 - 712) / PD685225 (residues 676 - 705) /
PD502558 (residues 699 - 758) / PD000915 (residues 716 - 770) / PD000348 (residues 771 - 926) /
PD000723 (residues 934 - 985) / PD371748 (residues 940 - 981)
SCOP:
SSF56672 - DNA/RNA polymerase /
SSF50630 - Acid protease /
SSF53098 - RNase H-like protein
SSF46919 - Integrase N-terminal Zn-binding domain /
SSF50122 - Integrase C-terminal DNA-binding domain
BLOCKS: P04585
Prosite: P04585
ProtoNet: P04585
ProtoMap: P04585
PRESAGE: P04585
Database of Interacting Proteins: P04585
ModBase: P04585
Swiss-2DPAGE: 2D gel
- BioAfrica Tools:
- - Pol Protein Data Mining Tool provides real-time analysis of HIV-1 Pol isolates
- - HIV Structure BLAST searches for similar HIV sequences that have known structures
- - HIV Proteomics Resource contains protein sequence and structure analysis tools
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Reviews and References: [TOP]
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- 1 - HIV Sequence Compendium 2000
- Kuiken CL, Foley B, Hahn B, Korber B, Marx PA, McCutchan F, Mellors JW, Mullins JI, Sodroski J, Wolinksy S.
- Theoretical Biol. & Biophys. Group, Los Alamos Nat Lab, LA-UR 01-3860 [Read it online: Compendium]
- 2 - Retroviruses
- Coffin JM, Hughes SH, Varmus HE.
- CD-ROM ed. (2002) Cold Spring Harbor Laboratory Press [Read it online: NCBI Bookshelf]
- 3 - Molecular Characteristics of HIV-1 Subtype C Viruses from KwaZulu-Natal, South Africa:
- Implications for Vaccine and Antiretroviral Control Strategies.
- Gordon M, De Oliveira T, Bishop K, Coovadia HM, Madurai L, Engelbrecht S, Janse van Rensburg E, Mosam A, Smith A, Cassol S.
- Journal of Virology 77(4): 2587-2599 (2003) [pubmed: 12551997]
- 4 - Characterization of ribosomal frameshifting in HIV-1 Gag-Pol expression.
- Jacks T, Power MD, Masiarz FR.
- Nature 331: 280-283 (1988) [pubmed: 2447506]
- 5 - Human immunodeficiency virus type 1 gag-pol frameshifting is dependent on
- mRNA secondary structure: Demonstration by expression in vivo.
- Parkin NT, Chamorro M, Varmus HE.
- J Virol 66: 5147-5151 (1992) [pubmed: 1321294]
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