EC - Retroviral ribonuclease H

  IntEnz view ENZYME view

IntEnz Enzyme Nomenclature


Accepted name:
retroviral ribonuclease H
Other names:
RT/RNase H
retroviral reverse transcriptase RNaseH
Systematic name:



Retroviral reverse transcriptase is a multifunctional enzyme responsible for viral replication. To perform this task the enzyme combines two distinct activities. The polymerase domain (EC, RNA-directed DNA polymerase) occupies the N-terminal two-thirds of the reverse transcriptase whereas the ribonuclease H domain comprises the C-terminal remaining one-third [13,14]. The RNase H domain of Moloney murine leukemia virus and Human immunodeficiency virus display two metal binding sites [15-17].

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Structural data: CSA , EC2PDB
CAS Registry Number: 9050-76-4
UniProtKB/Swiss-Prot: (71) [show] [UniProt]


  1. Schultz, S. J., Zhang, M., Champoux, J. J.
    Recognition of internal cleavage sites by retroviral RNases H.
    J. Mol. Biol. 344 : 635-652 (2004). [PMID: 15533434]
  2. Sarafianos, S. G., Das, K., Tantillo, C., Clark, A. D., Ding, J., Whitcomb, J. M., Boyer, P. L., Hughes, S. H., Arnold, E.
    Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA.
    EMBO J. 20 : 1449-1461 (2001). [PMID: 11250910]
  3. Rausch, J. W., Lener, D., Miller, J. T., Julias, J. G., Hughes, S. H., Le Grice, S. F.
    Altering the RNase H primer grip of human immunodeficiency virus reverse transcriptase modifies cleavage specificity.
    Biochemistry 41 : 4856-4865 (2002). [PMID: 11939780]
  4. Brehm, J. H., Mellors, J. W., Sluis-Cremer, N.
    Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance.
    Biochemistry 47 : 14020-14027 (2008). [PMID: 19067547]
  5. Schultz, S. J., Zhang, M., Kelleher, C. D., Champoux, J. J.
    Analysis of plus-strand primer selection, removal, and reutilization by retroviral reverse transcriptases.
    J. Biol. Chem. 275 : 32299-32309 (2000). [PMID: 10913435]
  6. DeStefano, J. J., Mallaber, L. M., Fay, P. J., Bambara, R. A.
    Determinants of the RNase H cleavage specificity of human immunodeficiency virus reverse transcriptase.
    Nucleic Acids Res. 21 : 4330-4338 (1993). [PMID: 7692401]
  7. Kati, W. M., Johnson, K. A., Jerva, L. F., Anderson, K. S.
    Mechanism and fidelity of HIV reverse transcriptase.
    J. Biol. Chem. 267 : 25988-25997 (1992). [PMID: 1281479]
  8. Palaniappan, C., Fuentes, G. M., Rodriguez-Rodriguez, L., Fay, P. J., Bambara, R. A.
    Helix structure and ends of RNA/DNA hybrids direct the cleavage specificity of HIV-1 reverse transcriptase RNase H.
    J. Biol. Chem. 271 : 2063-2070 (1996). [PMID: 8567660]
  9. Fu, T. B., Taylor, J.
    When retroviral reverse transcriptases reach the end of their RNA templates.
    J. Virol. 66 : 4271-4278 (1992). [PMID: 1376369]
  10. Beilhartz, G. L., Wendeler, M., Baichoo, N., Rausch, J., Le Grice, S., Gotte, M.
    HIV-1 reverse transcriptase can simultaneously engage its DNA/RNA substrate at both DNA polymerase and RNase H active sites: implications for RNase H inhibition.
    J. Mol. Biol. 388 : 462-474 (2009). [PMID: 19289131]
  11. Huang, H., Chopra, R., Verdine, G. L., Harrison, S. C.
    Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance.
    Science 282 : 1669-1675 (1998). [PMID: 9831551]
  12. Krug, M. S., Berger, S. L.
    Ribonuclease H activities associated with viral reverse transcriptases are endonucleases.
    Proc. Natl. Acad. Sci. USA 86 : 3539-3543 (1989). [PMID: 2471188]
  13. Champoux, J. J., Schultz, S. J.
    Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription.
    FEBS J. 276 : 1506-1516 (2009). [PMID: 19228195]
  14. Schultz, S. J., Champoux, J. J.
    RNase H activity: structure, specificity, and function in reverse transcription.
    Virus Res. 134 : 86-103 (2008). [PMID: 18261820]
  15. Goedken, E. R., Marqusee, S.
    Metal binding and activation of the ribonuclease H domain from moloney murine leukemia virus.
    Protein Eng. 12 : 975-980 (1999). [PMID: 10585503]
  16. Davies, J. F., Hostomska, Z., Hostomsky, Z., Jordan, S. R., Matthews, D. A.
    Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase.
    Science 252 : 88-95 (1991). [PMID: 1707186]
  17. Pari, K., Mueller, G. A., DeRose, E. F., Kirby, T. W., London, R. E.
    Solution structure of the RNase H domain of the HIV-1 reverse transcriptase in the presence of magnesium.
    Biochemistry 42 : 639-650 (2003). [PMID: 12534276]

[EC created 2009]