GAG-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.



Protease - p15
Reverse Transcriptase - p51
Reverse Transcriptase and RNase H - p66
RNase H - p15
Integrase - p31



ViralZone:HIV-1
PDB: none available
SwissProt: P04585 (HIV-1 HXB2 Pol)
Chime Tutorial: not available
Los Alamos HIV structure DB: not available
EMBL: K03455 [EMBL/GenBank/DDBJ]
BioAfrica: Pol Protein Data Mining Tool

Isoforms:

  • GAG-POL Polyprotein (1003 amino acids)
  • p160 - GAG-POL Polyprotein

Cleavage site:

Localization:

  • Virion
  • Cell cytoplasm

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

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

Genomic Location: [TOP]

Reference Sequences:

HIV-1 (HXB2): 

          10         20         30         40         50         60         70
           |          |          |          |          |          |          |
  FFREDLAFLQ GKAREFSSEQ TRANSPTRRE LQVWGRDNNS PSEAGADRQG TVSFNFPQVT LWQRPLVTIK
          80         90        100        110        120        130        140
           |          |          |          |          |          |          |
  IGGQLKEALL DTGADDTVLE EMSLPGRWKP KMIGGIGGFI KVRQYDQILI EICGHKAIGT VLVGPTPVNI 
         150        160        170        180        190        200        210
           |          |          |          |          |          |          |
  IGRNLLTQIG CTLNFPISPI ETVPVKLKPG MDGPKVKQWP LTEEKIKALV EICTEMEKEG KISKIGPENP 
         220        230        240        250        260        270        280
           |          |          |          |          |          |          |
  YNTPVFAIKK KDSTKWRKLV DFRELNKRTQ DFWEVQLGIP HPAGLKKKKS VTVLDVGDAY FSVPLDEDFR 
         290        300        310        320        330        340        350
           |          |          |          |          |          |          |
  KYTAFTIPSI NNETPGIRYQ YNVLPQGWKG SPAIFQSSMT KILEPFRKQN PDIVIYQYMD DLYVGSDLEI 
         360        370        380        390        400        410        420
           |          |          |          |          |          |          |
  GQHRTKIEEL RQHLLRWGLT TPDKKHQKEP PFLWMGYELH PDKWTVQPIV LPEKDSWTVN DIQKLVGKLN 
         430        440        450        460        470        480        490
           |          |          |          |          |          |          |
  WASQIYPGIK VRQLCKLLRG TKALTEVIPL TEEAELELAE NREILKEPVH GVYYDPSKDL IAEIQKQGQG 
         500        510        520        530        540        550        560
           |          |          |          |          |          |          |
  QWTYQIYQEP FKNLKTGKYA RMRGAHTNDV KQLTEAVQKI TTESIVIWGK TPKFKLPIQK ETWETWWTEY 
         570        580        590        600        610        620        630
           |          |          |          |          |          |          |
  WQATWIPEWE FVNTPPLVKL WYQLEKEPIV GAETFYVDGA ANRETKLGKA GYVTNRGRQK VVTLTDTTNQ 
         640        650        660        670        680        690        700
           |          |          |          |          |          |          |
  KTELQAIYLA LQDSGLEVNI VTDSQYALGI IQAQPDQSES ELVNQIIEQL IKKEKVYLAW VPAHKGIGGN 
         710        720        730        740        750        760        770
           |          |          |          |          |          |          |
  EQVDKLVSAG IRKVLFLDGI DKAQDEHEKY HSNWRAMASD FNLPPVVAKE IVASCDKCQL KGEAMHGQVD 
         780        790        800        810        820        830        840
           |          |          |          |          |          |          |
  CSPGIWQLDC THLEGKVILV AVHVASGYIE AEVIPAETGQ ETAYFLLKLA GRWPVKTIHT DNGSNFTGAT 
         850        860        870        880        890        900        910
           |          |          |          |          |          |          |
  VRAACWWAGI KQEFGIPYNP QSQGVVESMN KELKKIIGQV RDQAEHLKTA VQMAVFIHNF KRKGGIGGYS 
         920        930        940        950        960        970        980
           |          |          |          |          |          |          |
  AGERIVDIIA TDIQTKELQK QITKIQNFRV YYRDSRNPLW KGPAKLLWKG EGAVVIQDNS DIKVVPRRKA 
         990       1000        
           |          |  
  KIIRDYGKQM AGDDCVASRQ DED
      [download in fasta format]

Length: 1003 amino acids
Molecular Weight: 113779 Da
Protein Domains/Folds/Motifs: [TOP]

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)


Secondary Structure prediction:

Low Complexity Region - seg:


Antigenic Sites - EMBOSS:
Predicted Motifs: Printer-friendly version
N-glycosylation:
N-myristoylation:
Amidation:
Protein kinase C:
Casein kinase II:
Tyrosine kinase:
cAMP / cGMP kinase:
Cell attachment motif:
Asp Protease motif:
Asp Prot Retro motif:
Cysteine-rich Region:
Tryptophan-rich Region:
Zinc-finger CCHC motif:
Leucine Zipper motif:

Protein-Protein Interactions: [TOP]



Primary and Secondary Database Entries: [TOP]

Identifiers:

ViralZone: HIV-1
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
Reviews and References: [TOP]

Cite the resource by citing the following paper:
Doherty R et al. BioAfrica's HIV-1 Proteomics Resource: Combining protein data with bioinformatics tools. Retrovirology (2005), 9;2(1):18.

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]



Page last updated by Tulio de Oliveira.