RT- Reverse Transcriptase

HIV RT forms a heterodimer with RT/RNase H polyprotein and reverse transcribes viral RNA into DNA.




PDB-1RTD: HIV-1 (isolate UNKNOWN) RT mutant (UNKNOWN) and DNA complex - produced using SwissModel/SPDBV/POVray
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ViralZone:HIV-1
PDB: 1RTD (HIV-1 RT)
SwissProt: P04585 (HIV-1 HXB2 POL)
Chime Tutorial:  Online Macromolecular Museum
Los Alamos HIV structure DB: Reverse Transcriptase
EMBL: K03455 [EMBL/GenBank/DDBJ]
BioAfrica: Pol Protein Data Mining Tool


Isoforms:

  • p51 (440 amino acids) - Reverse Transcriptase
  • p66 (560 amino acids) - RT + RNase H

Cleavage site:

Localization:

  • Virion
  • Cell cytoplasm

Function:

  • RT makes a double-stranded DNA copy of the dimer of single-stranded RNA
  • RT has both RNA-dependant and DNA-dependant polymerase activity

Additional Information:

  • RT has low fidelity (high frequency of mutation)
  • viral DNA can be completely synthesized within 6 hours of viral entry
  • major functional species of polymerase is a heterodimer of p50 (Reverse Transcriptase) and p65 (Reverse Transcriptase - RNase H) (Ref. #4)
  • many cis-acting elements in viral RNA are required for the generation of viral DNA (Ref. #5)
  • TAR is a small RNA stem-loop structure located at 5'-end of viral RNA and is required for initiation of Reverse Transcriptase (Ref. #5)

Genomic Location: [TOP]

Reference Sequences:

HIV-1 (HXB2):

          10         20         30         40         50         60         70 
| | | | | | |
PISPIETVPV KLKPGMDGPK VKQWPLTEEK IKALVEICTE MEKEGKISKI GPENPYNTPV FAIKKKDSTK
80 90 100 110 120 130 140
| | | | | | |
WRKLVDFREL NKRTQDFWEV QLGIPHPAGL KKKKSVTVLD VGDAYFSVPL DEDFRKYTAF TIPSINNETP
150 160 170 180 190 200 210
| | | | | | |
GIRYQYNVLP QGWKGSPAIF QSSMTKILEP FRKQNPDIVI YQYMDDLYVG SDLEIGQHRT KIEELRQHLL
220 230 240 250 260 270 280
| | | | | | |
RWGLTTPDKK HQKEPPFLWM GYELHPDKWT VQPIVLPEKD SWTVNDIQKL VGKLNWASQI YPGIKVRQLC
290 300 310 320 330 340 350
| | | | | | |
KLLRGTKALT EVIPLTEEAE LELAENREIL KEPVHGVYYD PSKDLIAEIQ KQGQGQWTYQ IYQEPFKNLK
360 370 380 390 400 410 420
| | | | | | |
TGKYARMRGA HTNDVKQLTE AVQKITTESI VIWGKTPKFK LPIQKETWET WWTEYWQATW IPEWEFVNTP
430 440
| |
PLVKLWYQLE KEPIVGAETF
[download in fasta format]

Length: 440 amino acids (residues 155 to 585)
Molecular Weight: 51330 Da
Theoretical pI: 8.64


Protein Domains/Folds/Motifs: [TOP]

InterPro signature for RNA-directed DNA polymerase - IPR000477
InterPro signature for Reverse Transcriptase connection domain - IPR010659
InterPro signature for Reverse Transcriptase thumb domain - IPR010661


Secondary Structure predictions:

Low Complexity Regions - 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 & RT

SwissProt: P04585 (HIV-1 HXB2 POL)
EC: 2.7.7.49
EMBL: K03455; AAB50259.1 [EMBL/GenBank/DDBJ]

PIR: UNKNOWN
HIV: K03455; UNKNOWN$HXB2
InterPro: IPR008187UNKNOWN
Pfam: PF00558UNKNOWN
Prints: none
ProDom: PD000261 (1 - 62) / PD580497 (29 - 72) / PD492067 (63 - 105) / PD404869 (63 - 130)
PD000379 (106 - 148) / PD693134 (119 - 168) / PD513590 (121 - 161) / PD474846 (139 - 234)
PD000698 (235 - 296) / PD495523 (307 - 438)
SCOP:
SSF56672 DNA/RNA polymerase
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 - Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor.
Kohlstaedt LA, Wang J, Friedman JM.
Science 256: 1783-1790 (1992) [pubmed: 1377403]
5 - A critical role for the TAR element in promoting efficient human immunodeficiency virus type 1
reverse transcription.
Harrich D, Ulich C, Gaynor RB.
J Virol 70: 4017-4127 (1996) [pubmed: 8648739]
6 - [HIV RT Review] Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase:
implications for drug resistance.
Huang H, Chopra R, Verdine GL, Harrison SC.
Science 282(5394): 1669-1675 (1998) [pubmed: 9831551]
7 - [Website] An accurate look into HIV
Teresa Larsen
The Scripp Research Institute - Website: http://www.sdsc.edu/GatherScatter/GSsummer96/larsen.html
8 - [Website] HIV-1 RT
Kaylan Das
Rutgers University - Website: http://www.cabm.rutgers.edu/~kalyan/RT_imgs/index.html
9 - [Website] HIV Drug Resistance Database
Stanford
Website: http://hivdb.stanford.edu
10 - [Website] HIV Drug Resistance Database
Los Alamos National Labs
Website: http://resdb.lanl.gov/Resist_DB/default.htm



Page last updated by Tulio de Oliveira.